FoxO4 mediates macrophage M2 polarization by promoting LXA4R expression in an ovalbumin-induced allergic asthma model in mice
Main Article Content
Keywords
allergic asthma, FoxO4, LXA4R, macrophage M2 polarization
Abstract
Background: Asthma imposes a heavy burden due to its high prevalence. Forkhead box O4 (FoxO4) proteins participate in the modulation of cell progression. However, the role and mechanism of FoxO4 in asthma remains uncharted.
Methods: An allergic asthma model was constructed by the induction of ovalbumin and interleukin (IL)-4 in mice and monocyte/macrophage-like Raw264.7 cells, respectively. The role and mechanism of FoxO4 in asthma was determined by pathological staining, immunofluorescence assay, measurement of inflammatory cells in the blood, reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, and flow cytometry.
Results: Ovalbumin treatment triggered an obvious inflammatory cell infiltration with a prominent increase in F4/80+ cell numbers. The relative messenger RNA (mRNA) and protein expressions of FoxO4 were increased in both ovalbumin-induced mice and interleukin-4 (IL-4)-induced Raw264.7 cells. Inhibition of FoxO4 via AS1842856 reduced inflammatory cell infiltration, the number of Periodic Acid Schiff+ (PAS+) goblet cells, the numbers of inflammatory cells in the blood, and the airway resistance in ovalbumin-induced mice. Besides, interference of FoxO4 decreased the number of F4/80+CD206+ cells, and the relative protein expressions of CD163 and Arg1 in vivo and in vitro. Mechanically, suppression of FoxO4 diminished the relative mRNA and protein expressions of LXA4R in both ovalbumin-induced mice and IL-4-induced Raw264.7 cells. Overexpression of LXA4R reversed the outcomes caused by repression of FoxO4, including airway resistance, the number of F4/80+ cells, the proportion of CD206+ cells in ovalbumin-induced mice, and the proportion of F4/80+CD206+ cells in IL-4-induced Raw264.7 cells.
Conclusion: FoxO4/LXA4R axis mediated macrophage M2 polarization in allergic asthma.
References
1. Oliveira TB, Persigo ALK, Ferrazza CC, Ferreira ENN, Veiga ABG. Prevalence of asthma, allergic rhinitis and pollinosis in a city of Brazil: a monitoring study. Allergol Immunopathol (Madrid). 2020;48(6):537–44. 10.1016/j.aller.2020.03.010
2. Xepapadaki P, Adachi Y, Pozo Beltrán CF, El-Sayed ZA, Gómez RM, Hossny E, et al. Utility of biomarkers in the diagnosis and monitoring of asthmatic children. World Allergy Organ J. 2023;16(1):100727. 10.1016/j.waojou.2022.100727
3. Wu W, Bang S, Bleecker ER, Castro M, Denlinger L, Erzurum SC, et al. Multiview cluster analysis identifies variable corticosteroid response phenotypes in severe asthma. Am J Respir Crit Care Med. 2019;199(11):1358–67. 10.1164/rccm.201808-1543OC
4. Neto ACP, Solé D, Hirakata V, Schmid LS, Klock C, Barreto SSM. Risk factors for asthma in schoolchildren in Southern Brazil. Allergol Immunopathol (Madrid). 2020;48(3):237–43. 10.1016/j.aller.2019.07.003
5. Moghtaderi M, Ashraf MA, Teshnizi SH, Nabavizadeh H, Farjadian S, Fereidouni M. The level of allergens in dust samples collected from selected schools in Shiraz, Iran and its asthma-risk implications. Allergol Immunopathol (Madrid). 2020;48(1):90–4. 10.1016/j.aller.2019.05.005
6. Hallit S, Sacre H, Kheir N, Hallit R, Waked M, Salameh P. Prevalence of asthma, its correlates, and validation of the Pre-School Asthma Risk Factors Scale (PS-ARFS) among preschool children in Lebanon. Allergol Immunopathol (Madrid). 2021;49(1):40–9. 10.15586/aei.v49i1.25
7. Agache I, Eguiluz-Gracia I, Cojanu C, Laculiceanu A, Del Giacco S, Zemelka-Wiacek M, et al. Advances and highlights in asthma in 2021. Allergy. 2021;76(11):3390–407. 10.1111/all.15054
8. Soong W, Yoo B, Pazwash H, Holweg CTJ, Casale TB. Omalizumab response in patients with asthma by number and type of allergen. Ann Allergy Asthma Immunol. 2021;127(2):223–31. 10.1016/j.anai.2021.04.002
9. Hammad H, Lambrecht BN. The basic immunology of asthma. Cell. 2021;184(6):1469–85. 10.1016/j.cell.2021.02.016
10. Tosca MA, Girosi D, Sacco O, Bernardini R, Ciprandi G. Steroid-sparing effect of mepolizumab in children with severe eosinophilic nonallergic asthma. Allergol Immunopathol (Madrid). 2021;49(5):113–6. 10.15586/aei.v49i5.466
11. Mallol J, Riquelme C, Aguirre V, Martínez M, Gallardo A, Sánchez C, et al. Value of bronchial reversibility to salbutamol, exhaled nitric oxide and responsiveness to methacholine to corroborate the diagnosis of asthma in children. Allergol Immunopathol (Madrid). 2020;48(3):214–22. 10.1016/j.aller.2019.11.001
12. Côté A, Godbout K, Boulet LP. The management of severe asthma in 2020. Biochem Pharmacol. 2020;179:114112. 10.1016/j.bcp.2020.114112
13. Farhan M, Silva M, Xingan X, Huang Y, Zheng W. Role of FOXO transcription factors in cancer metabolism and angiogenesis. Cells. 2020;9(7):1586. 10.3390/cells9071586
14. Orea-Soufi A, Paik J, Bragança J, Donlon TA, Willcox BJ, Link W. FOXO transcription factors as therapeutic targets in human diseases. Trends Pharmacol Sci. 2022;43(12):1070–84. 10.1016/j.tips.2022.09.010
15. Link W. Introduction to FOXO biology. Methods Mol Biol. 2019;1890:1–9. 10.1007/978-1-4939-8900-3_1
16. Huang H, Tindall DJ. Dynamic FoxO transcription factors. J Cell Sci. 2007;120(Pt 15):2479–87. 10.1242/jcs.001222
17. Liu W, Li Y, Luo B. Current perspective on the regulation of FOXO4 and its role in disease progression. Cell Mol Life Sci. 2020;77(4):651–63. 10.1007/s00018-019-03297-w
18. Tian J, Ning J, Xu Y. Bioinformatics analysis of differentially expressed microRNAs in children with bronchial asthma]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2021;37(10):923–31.
19. Davis JS, Sun M, Kho AT, Moore KG, Sylvia JM, Weiss ST, et al. Circulating microRNAs and association with methacholine PC20 in the Childhood Asthma Management Program (CAMP) cohort. PLoS One. 2017;12(7):e0180329. 10.1371/journal.pone.0180329
20. Forno E, Zhang R, Jiang Y, Kim S, Yan Q, Ren Z, et al. Transcriptome-wide and differential expression network analyses of childhood asthma in nasal epithelium. J Allergy Clin Immunol. 2020;146(3):671–5. 10.1016/j.jaci.2020.02.005
21. Das UN. Essential fatty acids and their metabolites in the pathobiology of inflammation and its resolution. Biomolecules. 2021;11(12):1873. 10.3390/biom11121873
22. Goh J, Godson C, Brady HR, Macmathuna P. Lipoxins: pro-resolution lipid mediators in intestinal inflammation. Gastroenterology. 2003;124(4):1043–54. 10.1053/gast.2003.50154
23. Planagumà A, Kazani S, Marigowda G, Haworth O, Mariani TJ, Israel E, et al. Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma. Am J Respir Crit Care Med. 2008;178(6):574–82. 10.1164/rccm.200801-061OC
24. Chandrasekharan JA, Sharma-Walia N. Lipoxins: nature’s way to resolve inflammation. J Inflamm Res. 2015;8:181–92. 10.2147/JIR.S90380
25. Pérez-Novo CA, Watelet JB, Claeys C, Van Cauwenberge P, Bachert C. Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis. J Allergy Clin Immunol. 2005;115(6):1189–96. 10.1016/j.jaci.2005.02.029
26. El Kebir D, József L, Khreiss T, Pan W, Petasis NA, Serhan CN, et al. Aspirin-triggered lipoxins override the apoptosis-delaying action of serum amyloid A in human neutrophils: a novel mechanism for resolution of inflammation. J Immunol. 2007;179(1):616–22. 10.4049/jimmunol.179.1.616
27. Prieto P, Cuenca J, Través PG, Fernández-Velasco M, Martín-Sanz P, Boscá L. Lipoxin A4 impairment of apoptotic signaling in macrophages: implication of the PI3K/Akt and the ERK/Nrf-2 defense pathways. Cell Death Differ. 2010;17(7):1179–88. 10.1038/cdd.2009.220
28. Martini AC, Berta T, Forner S, Chen G, Bento AF, Ji RR, et al. Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection. J Neuroinflammation. 2016;13(1):75. 10.1186/s12974-016-0540-8
29. Fiore S, Maddox JF, Perez HD, Serhan CN. Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. J Exp Med. 1994;180(1):253–60. 10.1084/jem.180.1.253
30. Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN. Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med. 1997;185(9):1693–704. 10.1084/jem.185.9.1693
31. Kong X, Wu SH, Zhang L, Chen XQ. Roles of lipoxin A4 receptor activation and anti-interleukin-1β antibody on the toll-like receptor 2/mycloid differentiation factor 88/nuclear factor-κB pathway in airway inflammation induced by ovalbumin. Mol Med Rep. 2015;12(1):895–904. 10.3892/mmr.2015.3443
32. National Research Council (US) Committee for the Update of the Guide for the C, Use of Laboratory Animals. Guide for the care and use of laboratory animals, 8th ed. Washington, DC: National Academy of Sciences, National Academies Press (US); 2011. PMid: 21595115.
33. Jia S, Guo P, Lu J, Huang X, Deng L, Jin Y, et al. Curcumol ameliorates lung inflammation and airway remodeling via inhibiting the abnormal activation of the Wnt/β-Catenin pathway in chronic asthmatic mice. Drug Des Devel Ther. 2021;15:2641-2651. 10.2147/dddt.S292642.
34. Wang Q, Hong L, Chen M, Shi J, Lin X, Huang L, et al. Targeting M2 macrophages alleviates airway inflammation and remodeling in asthmatic mice via miR-378a-3p/GRB2 pathway. Front Mol Biosci. 2021;8:717969. 10.3389/fmolb.2021.717969
35. Nasab EM, Athari SM, Ghafarzade S, Nasab AM, Athari SS. Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma. Allergol Immunopathol (Madrid).48(6):646–53. 10.1016/j.aller.2020.01.003
36. Nie Y, Yang B, Hu J, Zhang L, Ma Z. Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway. Allergol Immunopathol (Madrid). 2021;49(6):73–9. 10.15586/aei.v49i6.499
37. Maru VP, Madkaikar M, Sattar S, Chauhan R, Devi RKS. Response of intra canal medicaments on viability and survival of SHEDs. J Clin Ped Dent. 2022;46(5):65–71.
38. Kozai K, Moreno-Irusta A, Iqbal K, Winchester ML, Scott RL, Simon ME, et al. The AKT1-FOXO4 axis reciprocally regulates hemochorial placentation. Development. 2023;150(2):dev201095. 10.1242/dev.201095.
39. Yang X, Zhang F, Liu X, Meng J, Du S, Shao J, et al. FOXO4 mediates resistance to oxidative stress in lens epithelial cells by modulating the TRIM25/Nrf2 signaling. Exp Cell Res. 2022;420(1):113340. 10.1016/j.yexcr.2022.113340
40. Zeng X, Peng Y, Wang Y, Kang K. C1q/tumor necrosis factor-related protein-3 (CTRP3) activated by forkhead box O4 (FOXO4) down-regulation protects retinal pericytes against high glucose-induced oxidative damage through nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling. Bioengineered. 2022;13(3):6080–91. 10.1080/21655979.2022.2031413
41. Yang W, He Q, Hu Z, Xie X. FOXO4 may be a biomarker of postmenopausal osteoporosis. Int J Gen Med. 2022;15:749–62. 10.2147/IJGM.S347416
42. Li L, Zhan Y, Xia H, Wu Y, Wu X, Chen S. Sevoflurane protects against intracerebral hemorrhage via microRNA-133b/FOXO4/BCL2 axis. Int Immunopharmacol. 2023;114:109453. 10.1016/j.intimp.2022.109453
43. Huang H, Dong J, Jiang J, Yang F, Zheng Y, Wang S, et al. The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease. Front Immunol. 2022;13:1090056. 10.3389/fimmu.2022.1090056
44. Choi HE, Kim DY, Choi MJ, Kim JI, Kim OH, Lee J, et al. Tranilast protects pancreatic β-cells from palmitic acid-induced lipotoxicity via FoxO-1 inhibition. Sci Rep. 2023;13(1):101. 10.1038/s41598-022-25428-3
45. Barkund S, Shah T, Ambatkar N, Gadgil M, Joshi K. FOXO3a gene polymorphism associated with asthma in Indian population. Mol Biol Int. 2015;2015:638515. 10.1155/2015/638515
46. Han K, Singh K, Rodman MJ, Hassanzadeh S, Wu K, Nguyen A, et al. Fasting-induced FOXO4 blunts human CD4(+) T helper cell responsiveness. Nat Metab. 2021;3(3):318–26. 10.1038/s42255-021-00356-0
47. Fricker M, Gibson PG. Macrophage dysfunction in the pathogenesis and treatment of asthma. Eur Respir J. 2017;50(3):1700196. 10.1183/13993003.00196-2017
48. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122(3):787–95. 10.1172/JCI59643
49. Liu G, Yang H. Modulation of macrophage activation and programming in immunity. J Cell Physiol. 2013;228(3):502–12. 10.1002/jcp.24157
50. Lee HY, Hur J, Kang JY, Rhee CK, Lee SY. MicroRNA-21 inhibition suppresses alveolar M2 macrophages in an ovalbumin-induced allergic asthma mice model. Allergy Asthma Immunol Res. 2021;13(2):312–29. 10.4168/aair.2021.13.2.312
51. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest. 2012;122(8):2741–8. 10.1172/JCI60325
52. Liu Y, Wei L, He C, Chen R, Meng L. Lipoxin A4 inhibits ovalbumin-induced airway inflammation and airway remodeling in a mouse model of asthma. Chem Biol Interact. 2021;349:109660. 10.1016/j.cbi.2021.109660
53. Chen LC, Tseng HM, Kuo ML, Chiu CY, Liao SL, Su KW, et al. A composite of exhaled LTB(4), LXA(4), FeNO, and FEV(1) as an “asthma classification ratio” characterizes childhood asthma. Allergy. 2018;73(3):627–34. 10.1111/all.13318
54. Barnig C, Levy BD. Lipoxin A4: a new direction in asthma therapy? Expert Rev Clin Immunol. 2013;9(6):491–3. 10.1586/eci.13.36
55. Jia G, Wang X, Wu W, Zhang Y, Chen S, Zhao J, et al. LXA4 enhances prostate cancer progression by facilitating M2 macrophage polarization via inhibition of METTL3. Int Immunopharmacol. 2022;107:108586. 10.1016/j.intimp.2022.108586
56. Yuan J, Lin F, Chen L, Chen W, Pan X, Bai Y, et al. Lipoxin A4 regulates M1/M2 macrophage polarization via FPR2-IRF pathway. Inflammopharmacology. 2022;30(2):487–98. 10.1007/s10787-022-00942-y
57. Kong X, Wu SH, Zhang L, Chen XQ. Pilot application of lipoxin A(4) analog and lipoxin A(4) receptor agonist in asthmatic children with acute episodes. Exp Ther Med. 2017;14(3):2284–90. 10.3892/etm.2017.4787
2. Xepapadaki P, Adachi Y, Pozo Beltrán CF, El-Sayed ZA, Gómez RM, Hossny E, et al. Utility of biomarkers in the diagnosis and monitoring of asthmatic children. World Allergy Organ J. 2023;16(1):100727. 10.1016/j.waojou.2022.100727
3. Wu W, Bang S, Bleecker ER, Castro M, Denlinger L, Erzurum SC, et al. Multiview cluster analysis identifies variable corticosteroid response phenotypes in severe asthma. Am J Respir Crit Care Med. 2019;199(11):1358–67. 10.1164/rccm.201808-1543OC
4. Neto ACP, Solé D, Hirakata V, Schmid LS, Klock C, Barreto SSM. Risk factors for asthma in schoolchildren in Southern Brazil. Allergol Immunopathol (Madrid). 2020;48(3):237–43. 10.1016/j.aller.2019.07.003
5. Moghtaderi M, Ashraf MA, Teshnizi SH, Nabavizadeh H, Farjadian S, Fereidouni M. The level of allergens in dust samples collected from selected schools in Shiraz, Iran and its asthma-risk implications. Allergol Immunopathol (Madrid). 2020;48(1):90–4. 10.1016/j.aller.2019.05.005
6. Hallit S, Sacre H, Kheir N, Hallit R, Waked M, Salameh P. Prevalence of asthma, its correlates, and validation of the Pre-School Asthma Risk Factors Scale (PS-ARFS) among preschool children in Lebanon. Allergol Immunopathol (Madrid). 2021;49(1):40–9. 10.15586/aei.v49i1.25
7. Agache I, Eguiluz-Gracia I, Cojanu C, Laculiceanu A, Del Giacco S, Zemelka-Wiacek M, et al. Advances and highlights in asthma in 2021. Allergy. 2021;76(11):3390–407. 10.1111/all.15054
8. Soong W, Yoo B, Pazwash H, Holweg CTJ, Casale TB. Omalizumab response in patients with asthma by number and type of allergen. Ann Allergy Asthma Immunol. 2021;127(2):223–31. 10.1016/j.anai.2021.04.002
9. Hammad H, Lambrecht BN. The basic immunology of asthma. Cell. 2021;184(6):1469–85. 10.1016/j.cell.2021.02.016
10. Tosca MA, Girosi D, Sacco O, Bernardini R, Ciprandi G. Steroid-sparing effect of mepolizumab in children with severe eosinophilic nonallergic asthma. Allergol Immunopathol (Madrid). 2021;49(5):113–6. 10.15586/aei.v49i5.466
11. Mallol J, Riquelme C, Aguirre V, Martínez M, Gallardo A, Sánchez C, et al. Value of bronchial reversibility to salbutamol, exhaled nitric oxide and responsiveness to methacholine to corroborate the diagnosis of asthma in children. Allergol Immunopathol (Madrid). 2020;48(3):214–22. 10.1016/j.aller.2019.11.001
12. Côté A, Godbout K, Boulet LP. The management of severe asthma in 2020. Biochem Pharmacol. 2020;179:114112. 10.1016/j.bcp.2020.114112
13. Farhan M, Silva M, Xingan X, Huang Y, Zheng W. Role of FOXO transcription factors in cancer metabolism and angiogenesis. Cells. 2020;9(7):1586. 10.3390/cells9071586
14. Orea-Soufi A, Paik J, Bragança J, Donlon TA, Willcox BJ, Link W. FOXO transcription factors as therapeutic targets in human diseases. Trends Pharmacol Sci. 2022;43(12):1070–84. 10.1016/j.tips.2022.09.010
15. Link W. Introduction to FOXO biology. Methods Mol Biol. 2019;1890:1–9. 10.1007/978-1-4939-8900-3_1
16. Huang H, Tindall DJ. Dynamic FoxO transcription factors. J Cell Sci. 2007;120(Pt 15):2479–87. 10.1242/jcs.001222
17. Liu W, Li Y, Luo B. Current perspective on the regulation of FOXO4 and its role in disease progression. Cell Mol Life Sci. 2020;77(4):651–63. 10.1007/s00018-019-03297-w
18. Tian J, Ning J, Xu Y. Bioinformatics analysis of differentially expressed microRNAs in children with bronchial asthma]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2021;37(10):923–31.
19. Davis JS, Sun M, Kho AT, Moore KG, Sylvia JM, Weiss ST, et al. Circulating microRNAs and association with methacholine PC20 in the Childhood Asthma Management Program (CAMP) cohort. PLoS One. 2017;12(7):e0180329. 10.1371/journal.pone.0180329
20. Forno E, Zhang R, Jiang Y, Kim S, Yan Q, Ren Z, et al. Transcriptome-wide and differential expression network analyses of childhood asthma in nasal epithelium. J Allergy Clin Immunol. 2020;146(3):671–5. 10.1016/j.jaci.2020.02.005
21. Das UN. Essential fatty acids and their metabolites in the pathobiology of inflammation and its resolution. Biomolecules. 2021;11(12):1873. 10.3390/biom11121873
22. Goh J, Godson C, Brady HR, Macmathuna P. Lipoxins: pro-resolution lipid mediators in intestinal inflammation. Gastroenterology. 2003;124(4):1043–54. 10.1053/gast.2003.50154
23. Planagumà A, Kazani S, Marigowda G, Haworth O, Mariani TJ, Israel E, et al. Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma. Am J Respir Crit Care Med. 2008;178(6):574–82. 10.1164/rccm.200801-061OC
24. Chandrasekharan JA, Sharma-Walia N. Lipoxins: nature’s way to resolve inflammation. J Inflamm Res. 2015;8:181–92. 10.2147/JIR.S90380
25. Pérez-Novo CA, Watelet JB, Claeys C, Van Cauwenberge P, Bachert C. Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis. J Allergy Clin Immunol. 2005;115(6):1189–96. 10.1016/j.jaci.2005.02.029
26. El Kebir D, József L, Khreiss T, Pan W, Petasis NA, Serhan CN, et al. Aspirin-triggered lipoxins override the apoptosis-delaying action of serum amyloid A in human neutrophils: a novel mechanism for resolution of inflammation. J Immunol. 2007;179(1):616–22. 10.4049/jimmunol.179.1.616
27. Prieto P, Cuenca J, Través PG, Fernández-Velasco M, Martín-Sanz P, Boscá L. Lipoxin A4 impairment of apoptotic signaling in macrophages: implication of the PI3K/Akt and the ERK/Nrf-2 defense pathways. Cell Death Differ. 2010;17(7):1179–88. 10.1038/cdd.2009.220
28. Martini AC, Berta T, Forner S, Chen G, Bento AF, Ji RR, et al. Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection. J Neuroinflammation. 2016;13(1):75. 10.1186/s12974-016-0540-8
29. Fiore S, Maddox JF, Perez HD, Serhan CN. Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. J Exp Med. 1994;180(1):253–60. 10.1084/jem.180.1.253
30. Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN. Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med. 1997;185(9):1693–704. 10.1084/jem.185.9.1693
31. Kong X, Wu SH, Zhang L, Chen XQ. Roles of lipoxin A4 receptor activation and anti-interleukin-1β antibody on the toll-like receptor 2/mycloid differentiation factor 88/nuclear factor-κB pathway in airway inflammation induced by ovalbumin. Mol Med Rep. 2015;12(1):895–904. 10.3892/mmr.2015.3443
32. National Research Council (US) Committee for the Update of the Guide for the C, Use of Laboratory Animals. Guide for the care and use of laboratory animals, 8th ed. Washington, DC: National Academy of Sciences, National Academies Press (US); 2011. PMid: 21595115.
33. Jia S, Guo P, Lu J, Huang X, Deng L, Jin Y, et al. Curcumol ameliorates lung inflammation and airway remodeling via inhibiting the abnormal activation of the Wnt/β-Catenin pathway in chronic asthmatic mice. Drug Des Devel Ther. 2021;15:2641-2651. 10.2147/dddt.S292642.
34. Wang Q, Hong L, Chen M, Shi J, Lin X, Huang L, et al. Targeting M2 macrophages alleviates airway inflammation and remodeling in asthmatic mice via miR-378a-3p/GRB2 pathway. Front Mol Biosci. 2021;8:717969. 10.3389/fmolb.2021.717969
35. Nasab EM, Athari SM, Ghafarzade S, Nasab AM, Athari SS. Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma. Allergol Immunopathol (Madrid).48(6):646–53. 10.1016/j.aller.2020.01.003
36. Nie Y, Yang B, Hu J, Zhang L, Ma Z. Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway. Allergol Immunopathol (Madrid). 2021;49(6):73–9. 10.15586/aei.v49i6.499
37. Maru VP, Madkaikar M, Sattar S, Chauhan R, Devi RKS. Response of intra canal medicaments on viability and survival of SHEDs. J Clin Ped Dent. 2022;46(5):65–71.
38. Kozai K, Moreno-Irusta A, Iqbal K, Winchester ML, Scott RL, Simon ME, et al. The AKT1-FOXO4 axis reciprocally regulates hemochorial placentation. Development. 2023;150(2):dev201095. 10.1242/dev.201095.
39. Yang X, Zhang F, Liu X, Meng J, Du S, Shao J, et al. FOXO4 mediates resistance to oxidative stress in lens epithelial cells by modulating the TRIM25/Nrf2 signaling. Exp Cell Res. 2022;420(1):113340. 10.1016/j.yexcr.2022.113340
40. Zeng X, Peng Y, Wang Y, Kang K. C1q/tumor necrosis factor-related protein-3 (CTRP3) activated by forkhead box O4 (FOXO4) down-regulation protects retinal pericytes against high glucose-induced oxidative damage through nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling. Bioengineered. 2022;13(3):6080–91. 10.1080/21655979.2022.2031413
41. Yang W, He Q, Hu Z, Xie X. FOXO4 may be a biomarker of postmenopausal osteoporosis. Int J Gen Med. 2022;15:749–62. 10.2147/IJGM.S347416
42. Li L, Zhan Y, Xia H, Wu Y, Wu X, Chen S. Sevoflurane protects against intracerebral hemorrhage via microRNA-133b/FOXO4/BCL2 axis. Int Immunopharmacol. 2023;114:109453. 10.1016/j.intimp.2022.109453
43. Huang H, Dong J, Jiang J, Yang F, Zheng Y, Wang S, et al. The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease. Front Immunol. 2022;13:1090056. 10.3389/fimmu.2022.1090056
44. Choi HE, Kim DY, Choi MJ, Kim JI, Kim OH, Lee J, et al. Tranilast protects pancreatic β-cells from palmitic acid-induced lipotoxicity via FoxO-1 inhibition. Sci Rep. 2023;13(1):101. 10.1038/s41598-022-25428-3
45. Barkund S, Shah T, Ambatkar N, Gadgil M, Joshi K. FOXO3a gene polymorphism associated with asthma in Indian population. Mol Biol Int. 2015;2015:638515. 10.1155/2015/638515
46. Han K, Singh K, Rodman MJ, Hassanzadeh S, Wu K, Nguyen A, et al. Fasting-induced FOXO4 blunts human CD4(+) T helper cell responsiveness. Nat Metab. 2021;3(3):318–26. 10.1038/s42255-021-00356-0
47. Fricker M, Gibson PG. Macrophage dysfunction in the pathogenesis and treatment of asthma. Eur Respir J. 2017;50(3):1700196. 10.1183/13993003.00196-2017
48. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122(3):787–95. 10.1172/JCI59643
49. Liu G, Yang H. Modulation of macrophage activation and programming in immunity. J Cell Physiol. 2013;228(3):502–12. 10.1002/jcp.24157
50. Lee HY, Hur J, Kang JY, Rhee CK, Lee SY. MicroRNA-21 inhibition suppresses alveolar M2 macrophages in an ovalbumin-induced allergic asthma mice model. Allergy Asthma Immunol Res. 2021;13(2):312–29. 10.4168/aair.2021.13.2.312
51. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest. 2012;122(8):2741–8. 10.1172/JCI60325
52. Liu Y, Wei L, He C, Chen R, Meng L. Lipoxin A4 inhibits ovalbumin-induced airway inflammation and airway remodeling in a mouse model of asthma. Chem Biol Interact. 2021;349:109660. 10.1016/j.cbi.2021.109660
53. Chen LC, Tseng HM, Kuo ML, Chiu CY, Liao SL, Su KW, et al. A composite of exhaled LTB(4), LXA(4), FeNO, and FEV(1) as an “asthma classification ratio” characterizes childhood asthma. Allergy. 2018;73(3):627–34. 10.1111/all.13318
54. Barnig C, Levy BD. Lipoxin A4: a new direction in asthma therapy? Expert Rev Clin Immunol. 2013;9(6):491–3. 10.1586/eci.13.36
55. Jia G, Wang X, Wu W, Zhang Y, Chen S, Zhao J, et al. LXA4 enhances prostate cancer progression by facilitating M2 macrophage polarization via inhibition of METTL3. Int Immunopharmacol. 2022;107:108586. 10.1016/j.intimp.2022.108586
56. Yuan J, Lin F, Chen L, Chen W, Pan X, Bai Y, et al. Lipoxin A4 regulates M1/M2 macrophage polarization via FPR2-IRF pathway. Inflammopharmacology. 2022;30(2):487–98. 10.1007/s10787-022-00942-y
57. Kong X, Wu SH, Zhang L, Chen XQ. Pilot application of lipoxin A(4) analog and lipoxin A(4) receptor agonist in asthmatic children with acute episodes. Exp Ther Med. 2017;14(3):2284–90. 10.3892/etm.2017.4787
Article Sidebar
Published
Jul 1, 2023
Article Details
How to Cite
Yu, T., Yu, Y., Ma, Y., & Chen, G. (2023). FoxO4 mediates macrophage M2 polarization by promoting LXA4R expression in an ovalbumin-induced allergic asthma model in mice. Allergologia Et Immunopathologia, 51(4), 19-30. https://doi.org/10.15586/aei.v51i4.8
Section
Original Articles
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
Yu, T., Yu, Y., Ma, Y., & Chen, G. (2023). FoxO4 mediates macrophage M2 polarization by promoting LXA4R expression in an ovalbumin-induced allergic asthma model in mice. Allergologia Et Immunopathologia, 51(4), 19-30. https://doi.org/10.15586/aei.v51i4.8