Central role of IL-6 receptor signal-transducing chain gp130 in activation of L-selectin adhesion by fever-range thermal stress

Qing Chen, Wan Chao Wang, Robert Bruce, Hong Li, David M Schleider, Michael J Mulbury, Mark D Bain, Paul K Wallace, Heinz Baumann, Sharon S Evans

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

The physiological benefit of the febrile response is poorly understood. Here we show that fever-range thermal stress enhances the function of the L-selectin lymphocyte homing receptor through an interleukin-6 (IL-6)-dependent signaling mechanism. Thermal stimulation of L-selectin adhesion in vitro and in vivo is mediated by engagement of the gp130 signal-transducing chain by IL-6 and a soluble form of the IL-6 receptor-alpha (sIL-6Ralpha) binding subunit. Thermal control of adhesion is maintained in IL-6-deficient mice through a gp130-dependent compensatory mechanism mediated by IL-6-related cytokines (i.e., oncostatin M [OSM], leukemia inhibitory factor [LIF], and IL-11). Combined biochemical and pharmacological inhibitor (PD98059, U0126, SB203580, SP600125) approaches positioned MEK1/ERK1-2, but not p38 MAPK or JNK, in the IL-6/sIL-6Ralpha signaling pathway upstream of activation of L-selectin/cytoskeletal interactions and L-selectin avidity/affinity. These results highlight a role for gp130-linked IL-6/sIL-6Ralpha transsignaling in amplifying lymphocyte trafficking during febrile inflammatory responses.

Original languageEnglish
Pages (from-to)59-70
Number of pages12
JournalImmunity
Volume20
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Animals
  • Antigens, CD/immunology
  • Cell Adhesion/physiology
  • Cytokine Receptor gp130
  • Hot Temperature
  • Humans
  • Interleukin-6/immunology
  • L-Selectin/physiology
  • Lymphocytes/physiology
  • MAP Kinase Kinase 1
  • Membrane Glycoproteins/immunology
  • Mice
  • Mitogen-Activated Protein Kinase 1/physiology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases/physiology
  • Mitogen-Activated Protein Kinases/physiology
  • Receptors, Interleukin-6/immunology
  • Signal Transduction/physiology

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