Unusual interleukin-4 and -13 signaling in human normal and tumor lung fibroblasts

Doucet, Christelle; Jasmin, C; Azzarone, Bruno

doi:10.1038/sj.onc.1203933

Cited by 36 publications

(35 citation statements)

References 35 publications

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“…It has been reported that lung myofibroblasts represent the differentiated counterpart of normal lung fibroblasts and express ␣-smooth muscle actin (32), and that lung myofibroblasts, in contrast to normal lung fibroblasts, constitutively express ␥ c (33). However, we found that HGF prepared from normal and inflamed regions expressed only a low level of ␣-smooth muscle actin, and that no differences in the expression were detected by immunohistochemistry (data not shown).…”

Section: Discussioncontrasting

confidence: 52%

Endogenous IL-15 Sustains Recruitment of IL-2Rβ and Common γ and IL-2-Mediated Chemokine Production in Normal and Inflamed Human Gingival Fibroblasts

Ozawa

Tada

Sugawara

et al. 2004

The Journal of Immunology

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We recently reported that anti-IL-15 neutralizing mAb has been shown to inhibit production of MCP-1 in response to IL-2 from normal human gingival fibroblasts (HGF), the major constituent of gingival tissue. In the present study, we examined the expression of IL-2R and IL-15R subunits in HGF from normal and inflamed regions and the role of endogenous IL-15 in IL-2-mediated signaling. Normal HGF expressed IL-2Rβ and common γ-chain (γc) but not IL-2Rα or IL-15Rα, whereas inflamed HGF expressed IL-2Rα, IL-15Rα, IL-2Rβ, and γc, as assessed by RT-PCR and flow cytometry. Exogenous IL-2 and IL-15 induced production of MCP-1 but not IL-8 in normal HGF, and induced the production of both chemokines in inflamed HGF. Both HGF constitutively transcribed the 48 aa-IL-15 isoform, and the isoform was not actively secreted but rather existed as a membrane-bound form. Pretreatment with anti-IL-15 neutralizing mAb for 24 h completely inhibited the production of MCP-1 induced by IL-2 and IL-15 and IL-2-induced phosphorylation of Jak 1 and 3 in HGF. The pretreatment and RNA interference targeted to IL-15 mRNA resulted in total inhibition of the IL-2Rβ and γc expression at mRNA and protein levels. Furthermore, excess amounts of IL-2 restored the inhibitory effect of anti-IL-15, inhibition of NF-κB abrogated the expression of IL-2Rβ and γc, and IL-2-induced-nuclear translocation of NF-κB was completely inhibited by the RNA interference in HGF. These results suggest that endogenous membrane-bound IL-15 sustains recruitment of IL-2Rβ and γc through activation of NF-κB in HGF.

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Section: Discussioncontrasting

confidence: 52%

Endogenous IL-15 Sustains Recruitment of IL-2Rβ and Common γ and IL-2-Mediated Chemokine Production in Normal and Inflamed Human Gingival Fibroblasts

Ozawa

Tada

Sugawara

et al. 2004

The Journal of Immunology

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“…2). IL-4 normally activates the Jak-Stat6 and the IRS-PI3K-AKT pathways; however, in some cases, it also activates the mitogen-activated protein kinase (Erk1/Erk2) pathway (10,11,15,(28)(29)(30). T98G cells contained persistently activated Erk1/Erk2, which was not further increased by IL-4 stimulation but completely ablated by U0126 that inhibits mitogen-activated protein kinase (Erk1/Erk2) kinase (Fig.…”

Section: Wwwaacrjournalsorgmentioning

confidence: 99%

“…3C). It is reported that activation of both PI3K-AKT and Jak/receptor tyrosine kinase/Stat3 pathways can regulate the expression of Bcl-2 family of antiapoptotic proteins depending on cellular context and cytokine/growth factor involved (29)(30)(31). To evaluate the relative contributions of these two pathways, we determined the effects of inhibition of (a) Jak activity by AG490 and (b) PI3K activity by LY294002 on the IL-4-dependent expression of Bcl-2, Bcl-x L , and Mcl-1.…”

Section: Wwwaacrjournalsorgmentioning

confidence: 99%

Aberrant Stat3 Signaling by Interleukin-4 in Malignant Glioma Cells: Involvement of IL-13Rα2

Rahaman¹,

Vogelbaum²,

Haque

2005

Cancer Research

106

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Interleukin (IL)-4 exhibits antitumor activity in rodent experimental gliomas, which is likely mediated by the actions of IL-4 on a variety of immune cells present in and around the tumor masses. Here, we show that IL-4, which activates Stat6 in normal human astrocytes and in a variety of other cells, induces an aberrant activation of Stat3 in glioblastoma multiforme (GBM) cells but not in normal human astrocytes. Previously, we have shown that autocrine IL-6 signaling induces a persistent activation of Stat3. Now, we show that

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“…CLIC4, a transport protein belonging to the chloride intracellular channel family, is expressed in TGF-β-treated primary breast fibroblasts but not in untreated primary breast fibroblasts [91]. Immunohistochemistry revealed that fibroblasts in non-cancerous breasts were devoid of CLIC4 expression; myofibroblasts present in breast [92], the breast [93], the liver [94], the lung [95], the prostate [96], and the pancreas [97]; they were located mainly at the invasion front. In line with this histological observation is the detection of a cluster of invasionspecific genes expressed in several cells of the host reaction [3,[98][99][100][101].…”

Section: Tgf-β Stimulates Angiogenesis In Vitro and In Vivomentioning

confidence: 99%

Role of tissue stroma in cancer cell invasion

Wever

Mareel

2003

The Journal of Pathology

927

813

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Unusual interleukin-4 and -13 signaling in human normal and tumor lung fibroblasts

Cited by 36 publications

References 35 publications

Endogenous IL-15 Sustains Recruitment of IL-2Rβ and Common γ and IL-2-Mediated Chemokine Production in Normal and Inflamed Human Gingival Fibroblasts

Endogenous IL-15 Sustains Recruitment of IL-2Rβ and Common γ and IL-2-Mediated Chemokine Production in Normal and Inflamed Human Gingival Fibroblasts

Aberrant Stat3 Signaling by Interleukin-4 in Malignant Glioma Cells: Involvement of IL-13Rα2

Role of tissue stroma in cancer cell invasion

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