Autophagy-related protein 5 knockdown alleviates the lipopolysaccharide-induced inflammatory response in RAW264.7 cells
Main Article Content
Keywords
autophagy-related protein 5, inflammatory responses, lipopolysaccharide, autophagy, inflammatory cytokines
Abstract
Lipopolysaccharide (LPS) is a potent inducer of cytokine-mediated inflammatory responses. Although autophagy and LPS-induced inflammatory responses are related, it is unclear how autophagy regulates these inflammatory responses. We aimed to determine the effect of autophagy on the LPS-induced myeloid differentiation factor 88 (MyD88)/mitogen-activated protein kinase (MAPK)/nuclear transcription factor kB (NF-κB) signaling pathways in the inflammatory responses. We also determined the effect of autophagy on the MyD88-independent signaling pathway activated by LPS. To determine the effect of autophagy on LPS-induced inflammatory responses in RAW264.7 cells, we examined various in vitro assays by knockdown of autophagy-related protein 5 (ATG5), a key component of autophagy. ATG5 knockdown suppressed pro-inflammatory cytokines, including interleukin 6 and tumor necrosis factor α in LPS-stimulated RAW264.7 cells. Moreover, ATG5 knockdown also affected both MyD88-dependent (MAPK/ NF-κB) and MyD88-independent (interferon regulatory factor 3) signaling pathways. This study demonstrates that dysfunctional autophagy suppresses LPS-induced inflammatory responses through both MyD88-dependent and MyD88-independent pathways in RAW264.7 cells. We propose that targeting autophagy regulation is a promising therapeutic approach for many diseases in which inflammatory responses contribute to their onset and progression of the disease.
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