title: Interferon gamma modulates the expression of neutrophil-derived chemokines.
abstract: 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.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kasama
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: P M
authors.initials: PM
authors.lastname: Lincoln
authors.forename: M D
authors.initials: MD
authors.lastname: Burdick
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007371:Interferon-gamma