Short-term heat exposure inhibits inflammation by abrogating recruitment of and nuclear factor-{kappa}B activation in neutrophils exposed to chemotactic cytokines

The American Journal of Pathology
Mira ChoiRalph Kettritz

Abstract

Cytokines, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-8 attract neutrophils into inflammatory sites. During emigration from the blood neutrophils interact with extracellular matrix proteins such as fibronectin. Fibronectin provides beta2-integrin co-stimulation, allowing GM-CSF and IL-8 to activate nuclear factor (NF)-kappaB, an effect that does not occur in suspension. We tested the hypothesis that exposure of mice to fever-like temperatures abrogates neutrophil recruitment and NF-kappaB activation in a mouse model of skin inflammation. Mice that were exposed to 40 degrees C for 1 hour showed strongly reduced GM-CSF- and IL-8-induced neutrophilic skin inflammation. In vitro heat exposure did not interfere with neutrophil adhesion or spreading on fibronectin but strongly inhibited migration toward both cytokines. Using specific inhibitors, we found that PI3-K/Akt was pivotal for neutrophil migration and that heat down-regulated this pathway. Furthermore, neutrophils on fibronectin showed abrogated NF-kappaB activation in response to GM-CSF and IL-8 after heat. In vivo heat exposure of mice followed by ex vivo stimulation of isolated bone marrow neutrophils confirmed these results. Fin...Continue Reading

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Citations

Oct 30, 2009·Current Opinion in Hematology·Raju C Reddy, Theodore J Standiford
May 5, 2011·Journal of Biomedicine & Biotechnology·Małgorzata BzowskaKrzysztof Guzik
Mar 1, 2017·Journal of Cellular and Molecular Medicine·Xiao-Fei ShenJun-Feng Du
Jul 9, 2017·Journal of the American Society of Nephrology : JASN·Mira ChoiRalph Kettritz
Jun 20, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shao-Lai ZhouJian Zhou

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