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 language | English |
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Pages (from-to) | 59-70 |
Number of pages | 12 |
Journal | Immunity |
Volume | 20 |
Issue number | 1 |
DOIs | |
State | Published - 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