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[Regulation of P38 and MKK6 on HMGB1 expression in alveolar macrophages induced by cyclic mechanical stretch.] [Ariticle in Chinese]

DING Ning, XIAO Hui, GAO Ju, XU Li-Xin, SHE Shou-Zhang

Departments of Anesthesiology and Out-patient clinic, Guangzhou First Municipal People’s Hospital, Guangzhou 510180, China； Department of Anesthesiology, the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, China

Abstract

The aim of the present study was to investigate the role of mitogen-activated protein kinase kinase 6 (MKK6)-P38 signaling pathway in cyclic mechanical stretch-induced high mobility group box 1 protein (HMGB1) expression in alveolar macrophages. In the study, Sprague-Dawley rats were anesthetized and then sacrificed by bloodletting. The lungs were lavaged six times with prechilled PBS. Alveolar macrophages were isolated from lavage samples. Recombinant plasmids were transfected into alveolar macrophages with liposome DOTAP. Alveolar macrophages transfected with P38(AF)/pGFP and MKK6b(E)/pGFP plasmids were taken as treated groups, while the groups that transfected with pcDNA3 plasmid and pGFP plasmid served as blank transfection group and control group, respectively. All the groups were then cultured in 6-well Bioflex cell culture plates and exposed to cyclic mechanical stretch at 20% elongation using Flexercell 4000T cell stretching unit. The results showed that the transfection of MKK6b(E) led to a marked increases in P38 kinase activity compared with control group. In contrast, the transfection of P38(AF) significantly inhibited P38 kinase activity. Compared with control group, HMGB1 protein and mRNA expression in MKK6b(E) transfected cells increased markedly, while HMGB1 expression in P38(AF) transfected cells decreased markedly. These results suggest that MKK6-P38 MAPK
signaling pathway regulates the expression of HMGB1 induced by cyclic mechanical stretch in alveolar macrophages.

Key words: p38 mitogen-activated protein kinase; mechanical stress; alveolar macrophage; high mobility group box 1

Received: 2008-10-17　　Accepted: 2008-12-22

Corresponding author: 许立新　　E-mail: gzxulixin@163.com

Citing This Article：

DING Ning, XIAO Hui, GAO Ju, XU Li-Xin, SHE Shou-Zhang. [Regulation of P38 and MKK6 on HMGB1 expression in alveolar macrophages induced by cyclic mechanical stretch.] [Ariticle in Chinese] . Acta Physiol Sin 2009; 61 (1): 49-55 (in Chinese with English abstract).