Interferon gamma modulates the expression of neutrophil-derived chemokines.
Specific cell recruitment to a site of acute inflammation is a crucial event characterized by the elicitation of mainly polymorphonuclear neutrophils (PMNs). Recently, it has been reported that PMNs can express and secrete chemotactic cytokines or chemokines, including IL-8, MIP-1 alpha, and MIP-1 beta. Moreover, PMN-derived chemokines are regulated by various soluble mediators, such as dexamethasone, prostaglandin E, classic chemoattractant factors (e.g., fMLP, C5a, leukotriene B4), IL-4, and IL-10. In this article we demonstrate that PMNs treated with IFN-gamma, a Th1-derived cytokine, can inhibit early mRNA expression for MIP-1 alpha, MIP-1 beta, and IL-8 (up to 8 hours post IFN-gamma addition), while augmenting their production at 24 hours post IFN-gamma addition. Furthermore, our studies demonstrate that one of the mechanisms for the activity of IFN-gamma in this system is via the autocrine activity of TNF-alpha. These data imply that PMN-derived chemokines are regulated by not only proinflammatory cytokines, including IL-1 beta and TNF-alpha, but also Th1- and Th2-derived cytokines, including IL-4, IL-10, and IFN-gamma. The role of these cytokine networks in regulating PMN-derived chemokines may play an important role in leukocyte elicitation during the initiation and maintenance of an inflammatory response.
Kasama
T
T
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Strieter
R M
RM
Lukacs
N W
NW
Lincoln
P M
PM
Burdick
M D
MD
Kunkel
S L
SL
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*
D016207:Cytokines; D007371:Interferon-gamma