Abstract
BackgroundThe uteruses of most dairy cattle are easily infected by bacteria, especially gram-negative bacteria, following parturition. Macrophages are important cells of the immune system and play a critical role in the inflammatory response. In addition, cortisol levels become significantly increased due to the stress of parturition in dairy cattle, and cortisol is among the most widely used and effective therapies for many inflammatory diseases. In this study, we assessed the anti-inflammatory effects and potential molecular mechanisms of cortisol using a Lipopolysaccharide (LPS)-induced RAW264.7 macrophage cell line.ResultsCortisol significantly suppressed the production of prostaglandin E2 (PGE2) and decreased the gene and protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Moreover, cortisol inhibited the mRNA expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and decreased IL-1β secretion in an LPS-treated RAW264.7 macrophage cell line. Moreover, we found that cortisol suppressed nuclear factor-kappa B (NF-κB) signaling in RAW264.7 macrophages stimulated with LPS. This suppression was mediated by the inhibition of IκBα degradation and NF-κB p65 phosphorylation. In addition, cortisol also suppressed the phosphorylation of mitogen-activated protein kinases (MAPK) such as extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase/stress-activated protein kinase (JNK).ConclusionsThese results suggest that high cortisol levels can attenuate LPS-induced inflammatory responses in the RAW264.7 macrophage cell line by regulating the NF-κB and MAPK signaling pathways.
Highlights
The uteruses of most dairy cattle are infected by bacteria, especially gram-negative bacteria, following parturition
We further investigated the ability of cortisol to inhibit the activation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and mitogen-activated protein kinases (MAPKs) to clarify the mechanism of its anti-inflammatory effects
Enzyme-linked immunosorbent assay (ELISA) kits for prostaglandin E2 (PGE2), IL-1β, IL-6, and TNFα were purchased from R & D Systems, Inc. (Minneapolis, MN, USA). β-actin, inducible nitric oxide (NO) synthase (iNOS), COX-2, extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-ERK1/2, p38, phospho-p38, Jun NH2-terminal kinase (JNK), phospho-JNK, NF-κB p65, phospho-NF-κB p65, IκBα and phospho-IκBα antibodies were purchased from Cell Signaling Technology (Boston, MA, USA)
Summary
The uteruses of most dairy cattle are infected by bacteria, especially gram-negative bacteria, following parturition. Macrophages are important cells of the immune system and play a critical role in the inflammatory response. We assessed the anti-inflammatory effects and potential molecular mechanisms of cortisol using a Lipopolysaccharide (LPS)-induced RAW264.7 macrophage cell line. Inflammation is a major risk factor for many diseases, and macrophages are important immune cells that act as Nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) are important signaling molecules in the Toll-like receptor (TLR) pathway [8, 9]. NF-κB plays an important role in regulating the inflammatory responses by increasing the expression of inflammatory mediators and pro-inflammatory cytokines such. Similar to NF-κB, the MAPK signaling pathways are involved in LPS-induced iNOS and COX-2 expression in activated macrophages [14]. Inhibition of the NF-κB and MAPK pathways may be a potential therapeutic approach to inflammatory injury
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