IL-4 regulation of IL-6 production involves Rac/Cdc42- and p38 MAPK-dependent pathways in keratinocytes

Wery-Zennaro, Sandrine; Zugaza, José L.; Letourneur, Martine; Bertoglio, Jacques; Pierre, Josiane

doi:10.1038/sj.onc.1203458

Cited by 59 publications

(50 citation statements)

References 75 publications

(65 reference statements)

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“…PKD also modulates the activities of several kinase signal transduction pathways, including activation of NF-B-dependent genes by acting downstream of IB degradation (43,44). The involvement of p38 MAPK and NF-B pathways in cytokine induction of IL-6 and IL-8 production have been well described in multiple cell types, including keratinocytes, acting either through enhancement of transcription or stabilization of mRNA (45)(46)(47)(48)(49). The results of our recent studies with Caco-2 cells suggest that one of the effects of icIL-1Ra1 could be inhibition of the p38 MAPK and NF-B pathways (30).…”

Section: Discussionmentioning

confidence: 99%

Intracellular IL-1 Receptor Antagonist Type 1 Inhibits IL-1-Induced Cytokine Production in Keratinocytes through Binding to the Third Component of the COP9 Signalosome

Banda

Guthridge

Sheppard

et al. 2005

The Journal of Immunology

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The IL-1 receptor antagonist (IL-1Ra) exists in four isoforms, three of which lack signal peptides and are primarily intracellular proteins. The biologic roles of the intracellular isoforms of IL-1Ra have remained unknown. The objective of these studies was to determine whether the major intracellular isoform of IL-1Ra 18-kDa type 1 (icIL-1Ra1), mediated unique functions inside cells. A yeast two-hybrid screen with HeLa cell lysates revealed specific binding of icIL-1Ra1, and not of the other IL-1Ra isoforms, to the third component of the COP9 signalosome complex (CSN3). This binding was confirmed by Far Western blot analysis, sedimentation on a glycerol gradient, glutathione pull-down experiments, and coimmunoprecipitation. In addition to binding specifically to CSN3, icIL-1Ra1 inhibited phosphorylation of p53, c-Jun, and IκB by the crude CSN-associated kinase and of p53 by recombinant protein kinase CK2 and protein kinase D, both associated with CSN3. The biologic relevance of the interaction between icIL-1Ra1 and CSN3 was demonstrated in the keratinocyte cell lines KB and A431, both possessing abundant CSN3. A431 cells exhibited high levels of icIL-1Ra1 but lacked both detectable IL-1α-induced IL-6 and IL-8 production and phosphorylation of p38 MAPK. KB cells displayed the opposite pattern which was reversed after transfection with icIL-1Ra1 mRNA. Inhibition of CSN3 or of icIL-1Ra1 production through gene knockdown with specific small interfering RNA in A431 cells each led to an inhibition of IL-1α-induced IL-6 and IL-8 production. Thus, icIL-1Ra1 exhibits unique anti-inflammatory properties inside cells through binding to CSN3 with subsequent inhibition of the p38 MAPK signal transduction pathway.

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Section: Discussionmentioning

confidence: 99%

Intracellular IL-1 Receptor Antagonist Type 1 Inhibits IL-1-Induced Cytokine Production in Keratinocytes through Binding to the Third Component of the COP9 Signalosome

Banda

Guthridge

Sheppard

et al. 2005

The Journal of Immunology

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“…p38 MAPK plays a key part in IL-6 production by many cytokines including TNF-a, IL-1b, and IL-4 (Miyazawa et al, 1998;Eliopoulos et al, 1999;Wery-Zennaro et al, 2000). TNF-a-mediated IL-6 induction occurs through TGF-b activating kinase 1 (TAK1) stimulation of NF-kB in which p38 MAPK acts as an activator of IkB kinases (Craig et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…It has been documented that IL-6 activation by IL-1b or TNF-a is mediated through the p38 MAPK pathway, and p38 MAPK participates in TGF-b1-induced gene expression (Hanafusa et al, 1999;Craig et al, 2000;Wery-Zennaro et al, 2000). Based on these reports, we explored whether the p38 MAPK signaling is involved in the TGF-b1-induced IL-6 expression in prostate cancer cells.…”

Section: Tgf-b1 Activates Il-6 Expression In Prostate Carcinoma Cellsmentioning

confidence: 99%

Transforming growth factor-β1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-κB, JNK, and Ras signaling pathways

et al. 2003

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“…A Cdc42 pulldown assay was performed using a GST fusion protein containing the Cdc42/Rac1 interactive binding domain of WASP (GST-CRIB-WASP). Cells kept in the absence of IL-2 for 48 h were stimulated with IL-2 for the indicated times and lysed as described previously (39). Cell lysates were centrifuged at 13,500 rpm for 15 min at 4°C and incubated for 1 h at 4°C with 50 g of GST fusion proteins coupled to glutathione-Sepharose beads.…”

Section: Methodsmentioning

confidence: 99%

Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell Proliferation

Arrizabalaga

Lacerda

Zubiaga

et al. 2012

Journal of Biological Chemistry

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Background: Rac1 has a relevant role in signal transduction pathways in T lymphocytes. Results: Rac1 GTPase associates with glycogen phosphorylase and modulates its enzymatic activity to trigger T cell proliferation. Conclusion: This study reveals a new role for Rac1 GTPase in cellular physiology, coordinating metabolism and proliferation. Significance: This new Rac1/PYGM pathway might be essential for an appropriate immune response.

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IL-4 regulation of IL-6 production involves Rac/Cdc42- and p38 MAPK-dependent pathways in keratinocytes

Cited by 59 publications

References 75 publications

Intracellular IL-1 Receptor Antagonist Type 1 Inhibits IL-1-Induced Cytokine Production in Keratinocytes through Binding to the Third Component of the COP9 Signalosome

Intracellular IL-1 Receptor Antagonist Type 1 Inhibits IL-1-Induced Cytokine Production in Keratinocytes through Binding to the Third Component of the COP9 Signalosome

Transforming growth factor-β1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-κB, JNK, and Ras signaling pathways

Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell Proliferation

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