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Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 expression in human tracheal smooth muscle cells.
Cell Signal. 2007 Jun; 19(6):1258-67.CS

Abstract

Lipopolysaccharide (LPS) has been shown to induce the expression of adhesion molecules on airway epithelial and smooth cells and contributes to inflammatory responses. Here, the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) pathways for LPS-induced vascular cell adhesion molecule (VCAM)-1 expression were investigated in HTSMCs. LPS-induced expression of VCAM-1 protein and mRNA in a time-dependent manner, was significantly inhibited by inhibitors of MEK1/2 (U0126), p38 (SB202190), and c-Jun-N-terminal kinase (JNK; SP600125). The involvement of p42/p44 MAPK and p38 in these responses was further confirmed by that transfection with small interference RNAs (siRNA) direct against MEK, p42, and p38 significantly attenuated LPS-induced VCAM-1 expression. Consistently, LPS-stimulated phosphorylation of p42/p44 MAPK and p38 was attenuated by pretreatment with U0126 or SB202190, and transfection with these siRNAs, respectively. In addition, LPS-induced VCAM-1 expression was significantly blocked by a specific NF-kappaB inhibitor helenalin. LPS-stimulated translocation of NF-kappaB into the nucleus and degradation of IkappaB-alpha was blocked by helenalin, U0126, SB202190, or SP600125. Moreover, the resultant enhancement of VCAM-1 expression increased the adhesion of polymorphonuclear cells to monolayer of HTSMCs which was blocked by pretreatment with helenalin, U0126, or SP600125 prior to LPS exposure. Taken together, these results suggest that in HTSMCs, activation of p42/p44 MAPK, p38, and JNK pathways, at least in part, mediated through NF-kappaB, is essential for LPS-induced VCAM-1 gene expression. These results provide new insight into the mechanisms of LPS action that bacterial toxins may promote inflammatory responses in the airway disease.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17303384

Citation

Lin, Wei-Ning, et al. "Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 Expression in Human Tracheal Smooth Muscle Cells." Cellular Signalling, vol. 19, no. 6, 2007, pp. 1258-67.
Lin WN, Luo SF, Lee CW, et al. Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 expression in human tracheal smooth muscle cells. Cell Signal. 2007;19(6):1258-67.
Lin, W. N., Luo, S. F., Lee, C. W., Wang, C. C., Wang, J. S., & Yang, C. M. (2007). Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 expression in human tracheal smooth muscle cells. Cellular Signalling, 19(6), 1258-67.
Lin WN, et al. Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 Expression in Human Tracheal Smooth Muscle Cells. Cell Signal. 2007;19(6):1258-67. PubMed PMID: 17303384.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 expression in human tracheal smooth muscle cells. AU - Lin,Wei-Ning, AU - Luo,Shue-Fen, AU - Lee,Chiang-Wen, AU - Wang,Chien-Chun, AU - Wang,Jong-Shyan, AU - Yang,Chuen-Mao, Y1 - 2007/01/19/ PY - 2006/12/20/received PY - 2007/01/02/accepted PY - 2007/2/17/pubmed PY - 2007/7/25/medline PY - 2007/2/17/entrez SP - 1258 EP - 67 JF - Cellular signalling JO - Cell. Signal. VL - 19 IS - 6 N2 - Lipopolysaccharide (LPS) has been shown to induce the expression of adhesion molecules on airway epithelial and smooth cells and contributes to inflammatory responses. Here, the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) pathways for LPS-induced vascular cell adhesion molecule (VCAM)-1 expression were investigated in HTSMCs. LPS-induced expression of VCAM-1 protein and mRNA in a time-dependent manner, was significantly inhibited by inhibitors of MEK1/2 (U0126), p38 (SB202190), and c-Jun-N-terminal kinase (JNK; SP600125). The involvement of p42/p44 MAPK and p38 in these responses was further confirmed by that transfection with small interference RNAs (siRNA) direct against MEK, p42, and p38 significantly attenuated LPS-induced VCAM-1 expression. Consistently, LPS-stimulated phosphorylation of p42/p44 MAPK and p38 was attenuated by pretreatment with U0126 or SB202190, and transfection with these siRNAs, respectively. In addition, LPS-induced VCAM-1 expression was significantly blocked by a specific NF-kappaB inhibitor helenalin. LPS-stimulated translocation of NF-kappaB into the nucleus and degradation of IkappaB-alpha was blocked by helenalin, U0126, SB202190, or SP600125. Moreover, the resultant enhancement of VCAM-1 expression increased the adhesion of polymorphonuclear cells to monolayer of HTSMCs which was blocked by pretreatment with helenalin, U0126, or SP600125 prior to LPS exposure. Taken together, these results suggest that in HTSMCs, activation of p42/p44 MAPK, p38, and JNK pathways, at least in part, mediated through NF-kappaB, is essential for LPS-induced VCAM-1 gene expression. These results provide new insight into the mechanisms of LPS action that bacterial toxins may promote inflammatory responses in the airway disease. SN - 0898-6568 UR - https://www.unboundmedicine.com/medline/citation/17303384/Involvement_of_MAPKs_and_NF_kappaB_in_LPS_induced_VCAM_1_expression_in_human_tracheal_smooth_muscle_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(07)00022-8 DB - PRIME DP - Unbound Medicine ER -