Additive Suppression of LPS-Induced IL-10 and TNF-α by Pre-treatment of Dexamethasone and SB203580 in a Murine Alveolar Macrophage Cell Line (MH-S)
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P38 inhibitors are potent anti-inflammatory agents with distinctive mechanism of action from corticosteroid; the potential combined use of both anti-inflammatory agents could be an effective treatment for inflammatory lung disease; however, the impact of such combination on the homeostasis of immune response was poorly understood. To investigate the combined effect of dexamethasone (DEX) and/or SB203580 on tumor necrosis factor (TNF)-α (pro-inflammatory) and interleukin (IL)-10 (anti-inflammatory) secretion in mouse alveolar macrophage cell line. Secreted TNF-α and IL-10 were measured by ELISA. Phosphorylated STAT3 were investigated using Western blotting and immunocytochemistry. Pre-treatment of DEX or SB203580 inhibited lipopolysaccharide (LPS)-stimulated IL-10, TNF-α secretion, and STAT3 phosphorylation. Combined use of both agents showed stronger inhibitory effect. Combining DEX and SB203580 showed strong inhibition on the LPS-induced IL-10 secretion and STAT3 phosphorylation, which might reflect a very important drawback from the combined use of both anti-inflammatory agents.
KEY WORDSP38MAPK inhibitors glucocorticoids signal transducers and activators of transcription-3 tumor necrosis factor-α interleukin-10
Conflict of interest
I certify that all my affiliations with or financial involvement in, within the past 5 years and foreseeable future, any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript are completely disclosed (e.g., employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, royalties).
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