Premium
MAP kinases differentially regulate the expression of macrophage hyperactivity after thermal injury
Author(s) -
Alexander Michelle,
Daniel Tanjanika,
Chaudry Irshad H.,
Schwacha Martin G.
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20050
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , kinase , signal transduction , burn injury , microbiology and biotechnology , proinflammatory cytokine , mediator , tumor necrosis factor alpha , cytokine , inflammation , medicine , chemistry , endocrinology , biology , surgery
Thermal injury increases the capacity of macrophages (Mϕ) to produce various inflammatory mediators, (i.e., Mϕ hyperactivity), which is believed to be involved in the development of subsequent immunosuppression, sepsis, and multiple organ failure. The signal transduction pathways involved in the expression of Mϕ hyperactivity post‐burn, however, remain to be clearly elucidated. To study this C57BL/6 female mice were subjected to a 25% TBSA burn and splenic Mϕs were isolated 7 days later. LPS‐stimulated inflammatory mediator production and MAPK expression (P38 ERK 1/2 and JNK) were determined. Burn injury increased LPS‐induced P38 MAPK, suppressed JNK activation and ERK 1/2 activation was unaltered. These changes in MAPK activation were paralleled by the increased production of PGE 2 , TNF‐α, IL‐1β, IL‐6, and IL‐10. Differential sensitivity to the inhibition of the MAPK pathways was observed with regard to the mediator evaluated and the presence or absence of burn injury. In general cytokine production in the burn group was in part resistant to the inhibition of a single MAPK pathway as compared with shams. Thus, burn injury increases cross‐talk between the MAPKs pathways, suggesting that alterations MAPK activation and signal transduction contribute to the development Mϕ hyperactivity post‐injury. J. Cell. Physiol. 201: 35–44, 2004. © 2004 Wiley‐Liss, Inc.