Abstract | INTRODUCTION: METHODS: In SNS-gp130(-/-) mice lacking gp130 selectively in sensory neurons and appropriate control littermates (SNS-gp130(flox/flox)), we induced antigen-induced arthritis (AIA), and assessed swelling, histopathological arthritis scores, pain scores, expression of CGRP in sensory neurons, serum concentrations of CGRP and cytokines, and the cytokine release from single cell suspensions from lymph nodes and spleens. In wild-type mice CGRP release was determined during development of AIA and, in cultured sensory neurons, upon IL-6 stimulation. RESULTS: Compared to SNS-gp130(flox/flox) mice SNS-gp130(-/-) mice showed significantly weaker initial swelling, reduced serum concentrations of CGRP, IL-6, and IL-2, no inflammation-evoked upregulation of CGRP in sensory neurons, but similar histopathological arthritis scores during AIA. During the initial swelling phase of AIA, CGRP was significantly increased in the serum, knee and spleen. In vitro, IL-6 augmented the release of CGRP from cultured sensory neurons. Upon antigen-specific restimulation lymphocytes from SNS-gp130(-/-) mice released more interleukin-17 and interferon-γ than lymphocytes from SNS-gp130(flox/flox) mice. In naive lymphocytes from SNS-gp130(flox/flox) and SNS-gp130(-/-) mice CGRP reduced the release of IL-2 (a cytokine which inhibits the release of interleukin-17 and interferon-γ). CONCLUSIONS:
IL-6 signaling in sensory neurons plays a role in the expression of arthritis. Selective deletion of gp130 signaling in sensory neurons reduces the swelling of the joint (most likely by reducing neurogenic inflammation) but increases some proinflammatory systemic cellular responses such as the release of interleukin-17 and interferon-γ from lymphocytes upon antigen-specific restimulation. Thus IL-6 signaling in sensory neurons is not only involved in pain generation but also in the coordination of the inflammatory response.
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Authors | Matthias Ebbinghaus, Gisela Segond von Banchet, Julia Massier, Mieczyslaw Gajda, Rolf Bräuer, Michaela Kress, Hans-Georg Schaible |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 17
Pg. 334
(Nov 21 2015)
ISSN: 1478-6362 [Electronic] England |
PMID | 26590032
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens
- Il6st protein, mouse
- Interleukin-6
- interleukin-6, mouse
- Cytokine Receptor gp130
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Topics |
- Animals
- Antigens
(toxicity)
- Arthritis, Experimental
(chemically induced, metabolism, pathology)
- Cytokine Receptor gp130
(deficiency)
- Female
- Interleukin-6
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nociceptors
(drug effects, metabolism, pathology)
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