Low-level laser therapy suppresses the oxidative stress-induced glucocorticoids resistance in U937 cells: Relevance to cytokine secretion and histone deacetylase in alveolar macrophages
•LLLT restores the responsiveness of U937 cells to the corticoid.•LLLT increases the histone deacetylase activity in oxidative stress condition.•LLLT effect on U937 cells in oxidative stress is cAMP dependent.•LLLT acts on PI3K activity in U937 cells like the cAMP elevating agents.
Oxidative stress is present in severe asthma and contributes to the low response to corticoids through the downregulation of histone deacetylase (HDAC) and the increase of cytokines. Low-level laser therapy (LLLT) has been proven to be an anti-inflammatory. Thus, we investigated the laser effect on lipopolysaccharide (LPS)-induced cytokine secretion and HDAC activity in U937 cells under oxidative stress. U937 cells activated with oxidative stress were treated with dexamethasone (dexa) or laser. Cytokines and phosphoinositide 3-kinase (PI3K) were measured by ELISA whilst the HDAC was detected through colorimetric assay. LPS activated- U937 cells cytokines secretion increased with H2O2 (hydrogen peroxide) as well as with TSA (trichostatin). The HDAC activity in activated U937 cells was decreased. LLLT and dexa inhibited the LPS-stimulated U937 cells cytokines, but dexa effect disappeared with H2O2. With TSA, the LLLT was less effective on H2O2/LPS stimulated- U937 cells cytokines. Dexa failed on H2O2/LPS- induced HDAC, while LLLT restored the HDAC and the dexa effect. LLLT plus prostaglandin E2 (PGE2) increased cyclic adenosine monophosphate (cAMP) and potentiated the laser action on oxidative stress-induced cytokine. LLLT reduced the PI3K and its effects on cytokine and HDAC was suppressed with LY294002. In situations of corticoid resistance, LLLT acts decreasing the cytokines and HDAC through the activation of the protein kinase A via the inhibition of PI3K.
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Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 130, 5 January 2014, Pages 327–336