Expression of interleukin‐22 in rheumatoid arthritis: Potential role as a proinflammatory cytokine

Ikeuchi, Hidekazu; Kuroiwa, Takashi; Hiramatsu, Noriyuki; Kaneko, Yoriaki; Hiromura, Keiju; Ueki, Kazue; Nojima, Yoshihisa

doi:10.1002/art.20965

Cited by 354 publications

(302 citation statements)

References 20 publications

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“…This result stands in contrast to the argument that IL-22 has a proinflammatory function (45)(46)(47). The evidence for the latter comes primarily from studies describing IL-22-mediated induction of defensin genes (45,47).…”

Section: Anti-inflammatory Signals Generated By the Il-27 And Il-22 Rmentioning

confidence: 64%

General Nature of the STAT3-Activated Anti-Inflammatory Response

Kasmi

Holst²,

Coffre

et al. 2006

The Journal of Immunology

202

179

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Although many cytokine receptors generate their signals via the STAT3 pathway, the IL-10R appears unique in promoting a potent anti-inflammatory response (AIR) via STAT3 to antagonize proinflammatory signals that activate the innate immune response. We found that heterologous cytokine receptor systems that activate STAT3 but are naturally refractory (the IL-22R), or engineered to be refractory (the IL-6, leptin, and erythropoietin receptors), to suppressor of cytokine signaling-3-mediated inhibition activate an AIR indistinguishable from IL-10. We conclude that the AIR is a generic cytokine signaling pathway dependent on STAT3 but not unique to the IL-10R.

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Section: Anti-inflammatory Signals Generated By the Il-27 And Il-22 Rmentioning

confidence: 64%

General Nature of the STAT3-Activated Anti-Inflammatory Response

Kasmi

Holst²,

Coffre

et al. 2006

The Journal of Immunology

202

179

View full text Add to dashboard Cite

show abstract

“…Of note, other than STAT3, IL-22 is also known to activate other signaling pathways such as the three major MAPK pathways, ERK1/2, JNK and p38 kinase pathways. 22,35,36 These pathways, which have been implicated in transformation and tumor progression in many human cancers, 37,39 were confirmed to be activated by IL-22 in ALK þ ALCL cell lines. NPM-ALK is also a known activator of the ERK1/2 signaling pathway and has been shown to enhance cell proliferation and survival.…”

Section: Discussionmentioning

confidence: 94%

Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma

et al. 2008

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“…This, however, does not exclude the constitutive production of other soluble factors that might be involved in the constitutive expression of chemokines or other mediators of inflammation that were not analyzed in the current study. Indeed, earlier studies have demonstrated the constitutive production of IL-6, IL-11 (10), or IL-22 (48) by RASFs.…”

Section: Discussionmentioning

confidence: 98%

Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis

Hintzen¹,

Quaiser²,

Pap³

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP-4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.Methods. Using RNase protection assays and enzyme-linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/ MCP-1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.Results. The interleukin-6 (IL-6)-type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL-6 nor tumor necrosis factor ␣ could stimulate the expression of CCL13 in synovial fibroblasts; IL-1␤ was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT-5, ERK-1/2, and p38 as critical factors involved in OSM-dependent transcription and messenger RNA stabilization of CCL13.Conclusion. In contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up-regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM-induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue-specific imprinting of different fibroblasts during development.

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Expression of interleukin‐22 in rheumatoid arthritis: Potential role as a proinflammatory cytokine

Abstract: Conclusion. These data suggest that IL-22, produced by synovial fibroblasts and macrophages, promotes inflammatory responses in RA synovial tissues by inducing the proliferation and chemokine production of synovial fibroblasts.

Cited by 354 publications

References 20 publications

General Nature of the STAT3-Activated Anti-Inflammatory Response

General Nature of the STAT3-Activated Anti-Inflammatory Response

Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma

Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis

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