IL‐1β induces VCAM‐1 expression via activation of Akt and CaM kinaseII and modifications of HAT and HDAC4 in human tracheal smooth muscle cells

Abstract

During airway inflammatory processes, up‐regulation of VCAM‐1 may enhance adhesion between leukocytes and human tracheal smooth muscle cells (HTSMCs). We have previously demonstrated that IL‐1β‐induced VCAM‐1 expression is mediated by MAPKs and NF‐κB activation in HTSMCs. In addition, phosphorylation of Akt and CaM kinase II has been shown to involve in HAT and HDAC4 activation. Here, we investigated whether these mechanisms participating in IL‐1β‐induced VCAM‐1 expression and neutrophils adhesion. IL‐1β significantly induced HTSMCs‐neutrophils adhesion, which was inhibited by selective inhibitors of Src (PP1), EGFR (AG1478), PI3K (LY294002), calcium (BAPTA/AM), PI‐PLC (U73122), PKC (GÖ6976, rottlerin, and Ro31‐8220), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (curcumin), and HDAC (trichostatin A) or transfection with siRNAs of Src, Akt, PKCα, PKCμ, CaM kinase II, and HDAC4. Moreover, IL‐1β induced Akt and CaM kinase II phosphorylation mediated through Src/EGFR/PI3K and PLC/calcium/CaM pathways, respectively. Activation of Akt and CaMKII may eventually lead to the acetylation of histone residues and phosphorylation of histone de‐acetylase. These findings suggested that IL‐1β‐induced VCAM‐1 expression via multiple signaling pathways. Blockade of these pathways may be selectively targeted to reduce neutrophils adhesion via VCAM‐1 suppression and attenuation of the inflammatory responses in airway diseases.