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Signaling mechanisms of interleukin‐4‐induced pro‐inflammatory pathways in human vascular endothelial cells
Author(s) -
Lee Yong Woo,
Hirani Anjali A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1186-c
Subject(s) - signal transduction , microbiology and biotechnology , mapk/erk pathway , chemokine , pi3k/akt/mtor pathway , janus kinase , p38 mitogen activated protein kinases , jak stat signaling pathway , biology , cancer research , inflammation , immunology , tyrosine kinase
It has been proposed that two major signal transduction pathways such as Janus kinase (JAK)‐signal transducers and activators of transcription (STAT) and phosphoinositide‐3 kinase (PI3K) are involved in the signaling cascade initiated by IL‐4. Emerging evidence has also established the p38 mitogen‐activated protein kinase (MAPK) pathway as one element of the IL‐4 signaling cascade. The present study was designed to examine the hypothesis that interleukin‐4 (IL‐4) may induce pro‐inflammatory pathways through activation of p38 MAPK in human vascular endothelial cells (HUVEC). The quantitative real‐time RT‐PCR showed that selective inhibitors for JAK/STAT and PI3K signaling pathways significantly attenuated overexpression of pro‐inflammatory mediators in IL‐4‐stimulated HUVEC. In addition, p38 MAP kinase inhibitor SB202190 significantly and dose‐dependently inhibited IL‐4‐mediated up‐regulation of mRNA and protein expression of pro‐inflammatory cytokine (interleukin‐6), chemokine (monocyte chemoattractant protein‐1) and adhesion molecules (vascular cell adhesion molecule‐1 and E‐selectin) in HUVEC. These results provide new evidence to indicate that IL‐4 can induce pro‐inflammatory vascular environment through the p38 MAPK‐mediated signaling pathways. These data may contribute to understanding the cellular and molecular signaling mechanisms involved in IL‐4‐mediated progression of atherosclerosis and development of therapeutic strategies for the prevention of atherosclerotic lesion (This work was supported by the American Heart Association Ohio Valley Affiliate).