Human recombinant interleukin‐1α‐mediated stimulation of procollagenase production and suppression of biosynthesis of tissue inhibitor of metalloproteinases in rabbit uterine cervical fibroblasts

Ito, Akira; Goshowaki, Hideko; Sato, Takashi; Mori, Yo; Yamashita, Kyoko; Hayakawa, Taro; Nagase, Hideaki

doi:10.1016/0014-5793(88)80109-1

Cited by 40 publications

(20 citation statements)

References 25 publications

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“…Interestingly, IL-6 has also been shown to enhance the synthesis of TGF-␤ (50), which might reinforce these feedback circuits. The contradictory results, which have shown that IL-1, depending on the conditions, can either stimulate or inhibit the synthesis of TIMP (17,19), suggest interactions and indirect effects through other cytokine receptors systems, including IL-6/IL-6R␣/sIL-6R␣.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, catabolic cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-␣ (TNF-␣), the main promoters of MMPs synthesis and matrix degradation, have a marked inhibitory effect on TIMP-1 expression by chondrocytes, although some results have shown that IL-1, depending on the conditions, can either stimulate or inhibit the synthesis of TIMP-1 (15)(16)(17)(18)(19). IL-6 was initially considered a pro-inflammatory cytokine like TNF-␣ and IL-1, because of its IL-1-like effects on immune and hepatic cells.…”

mentioning

confidence: 99%

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Interleukin (IL)-6 and Its Soluble Receptor Induce TIMP-1 Expression in Synoviocytes and Chondrocytes, and Block IL-1-induced Collagenolytic Activity

Silacci¹,

Dayer²,

Desgeorges³

et al. 1998

Journal of Biological Chemistry

100

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To define the potential role of interleukin-6 (IL-6) and its soluble receptor ␣ in cartilage metabolism, we analyzed their effects on tissue inhibitor of metalloproteases (TIMP) synthesis by synoviocytes and chondrocytes. TIMP-1 production by isolated human articular synovial fibroblasts and chondrocytes, stimulated by IL-6 and/or its soluble receptor, was first assayed by specific enzyme-linked immunosorbent assay; the slight stimulatory effect of IL-6 on TIMP-1 production by both types of cells was markedly amplified by the addition of soluble receptor, the maximal secretion being observed only at 96 h. TIMP-1 mRNA expression, determined by ribonuclease protection assay, was induced by IL-6 together with its soluble receptor, but TIMP-2 and -3 mRNAs were not affected by these factors. A specific neutralizing antibody abolished the effects of the soluble receptor. Finally, supernatant from synoviocytes stimulated by IL-6 plus its soluble receptor blocked almost completely the collagenolytic activity of supernatant from IL-1-induced synoviocytes. These observations indicate that IL-6 and its soluble receptor have a protective role in the metabolism of cartilage. Given the high levels of soluble receptor in synovial fluid and the marked induction of IL-6 by IL-1 or TNF-␣, it is likely that IL-6 and its soluble receptor are critical in controlling the catabolic effects of pro-inflammatory cytokines.Tissue inhibitors of metalloproteases (TIMPs) 1 are important and specific inhibitors of matrix metalloproteases (MMPs) activity (1). These two classes of molecules play a crucial role in the fine regulation of extracellular matrix turnover, which is altered in most pathological states associated with abnormal extracellular matrix formation (i.e. fibrotic diseases) or tissue destruction (i.e. rheumatoid arthritis). TIMP proteins can bind either to the active site of MMPs, thus blocking access to the substrate, or to the precursor form, blocking further activation.So far, the sequences coding for four human TIMPs (TIMP-1, -2, and -3 and, more recently, TIMP-4) have been identified (1-11). The expression of TIMP-1 proved to be both constitutive and inducible, whereas TIMP-2 appeared to be widely expressed but not inducible (1,12). A recent study indicates that TIMP-3 expression is also constitutive and inducible (13).TIMP-1 expression in differentiated chondrocytes and fibroblasts has been shown to regulated by a few growth factors or cytokines, among which transforming growth factor-␤ (TGF-␤) is considered to be the most important inducer (1,14). On the other hand, catabolic cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-␣ (TNF-␣), the main promoters of MMPs synthesis and matrix degradation, have a marked inhibitory effect on TIMP-1 expression by chondrocytes, although some results have shown that IL-1, depending on the conditions, can either stimulate or inhibit the synthesis of TIMP-1 (15-19). IL-6 was initially considered a pro-inflammatory cytokine like TNF-␣ and IL-1, because of its IL-1-like eff...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Interleukin (IL)-6 and Its Soluble Receptor Induce TIMP-1 Expression in Synoviocytes and Chondrocytes, and Block IL-1-induced Collagenolytic Activity

Silacci¹,

Dayer²,

Desgeorges³

et al. 1998

Journal of Biological Chemistry

100

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“…This process of apoptosis in ripening cervices resembles the deletion of cell popula tions that occurs in normal development and metamor phosis [28,29]. Furthermore, apoptosis is regulated by hormones [10,11,13,14], paracrines and cytokines [24][25][26][27], Interestingly, the onset of labor and cervical ripening has been shown to be regulated by estradiol and progester one antagonists [30][31][32][33], adrenocorticotropin [34] and prostaglandins [35].…”

Section: Discussionmentioning

confidence: 99%

“…Upon the death of cervical cells and subsequent infiltration of monocytes, proteolytic enzymes are re leased from these cells [24][25][26][27] that further degrade inter cellular materials including myosin and actin. These pro teases which modify the specific protease inhibitors may initiate the hydrolysis of connective tissues and lead to the softening of the cervix [24][25][26][27],…”

Section: Discussionmentioning

confidence: 99%

Apoptosis in the Cervix of Pregnant Rats in Association with Cervical Softening

Leppert

Yu²

1994

Gynecol Obstet Invest

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Cervical ripening in gestation occurs spontaneously in a timely but species specific fashion as if it were genetically programmed. This study shows that the numbers of dying smooth muscle cells in the cervix increased along with cervical softening in pregnant rats from day 12 of gestation to day 21. The morphological characteristics of the chromatin cleavage in apoptosis are identified. Internucleosomal DNA fragments in the DNA preparations as well as the ladder pattern of double-stranded DNA observed on gel electrophoresis are observed. The deletion and decrease of the cell population in the cervices was demonstrated by a decrease of total DNA in these tissues. The interesting possibility is raised that programmed smooth muscle cell death in the cervix may be involved in the processes of the cervical ripening.

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“…These interleukins are primarily recognized for their capacity to regulate innate and cognate immune responses, and are produced by a variety of cells participating in host defense against noxious agents [Dinarello, 1994b]. IL-1 has also been shown to regulate connective tissue metabolism, in particular by promoting degradation of ECM [Ito et al, 1988;Qwarnstrom et al, 1989]. Monocytes and macrophages are the principal source of IL-1 but resident cells such as keratinocytes, fibroblasts and endothelial cells can also produce IL-1 [Dinarello, 1994a].…”

mentioning

confidence: 99%

Inhibition of connective tissue growth factor/CCN2 expression in human dermal fibroblasts by interleukin‐1α and β

Nowinski

Koskela²,

Kiwanuka

et al. 2010

J of Cellular Biochemistry

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Connective tissue growth factor (CTGF/CCN2) is a matricellular protein induced by transforming growth factor (TGF)-beta and intimately involved with tissue repair and overexpressed in various fibrotic conditions. We previously showed that keratinocytes in vitro downregulate TGF-beta-induced expression of CTGF in fibroblasts by an interleukin (IL)-1 alpha-dependent mechanism. Here, we investigated further the mechanisms of this downregulation by both IL-1alpha and beta. Human dermal fibroblasts and NIH 3T3 cells were treated with IL-1alpha or beta in presence or absence of TGF-beta1. IL-1 suppressed basal and TGF-beta-induced CTGF mRNA and protein expression. IL-1alpha and beta inhibited TGF-beta-stimulated CTGF promoter activity, and the activity of a synthetic minimal promoter containing Smad 3-binding CAGA elements. Furthermore, IL-1alpha and beta inhibited TGF-beta-stimulated Smad 3 phosphorylation, possibly linked to an observed increase in Smad 7 mRNA expression. In addition, RNA interference suggested that TGF-beta activated kinase1 (TAK1) is necessary for IL-1 inhibition of TGF-beta-stimulated CTGF expression. These results add to the understanding of how the expression of CTGF in human dermal fibroblasts is regulated, which in turn may have implications for the pathogenesis of fibrotic conditions involving the skin.

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Human recombinant interleukin‐1α‐mediated stimulation of procollagenase production and suppression of biosynthesis of tissue inhibitor of metalloproteinases in rabbit uterine cervical fibroblasts

Cited by 40 publications

References 25 publications

Interleukin (IL)-6 and Its Soluble Receptor Induce TIMP-1 Expression in Synoviocytes and Chondrocytes, and Block IL-1-induced Collagenolytic Activity

Interleukin (IL)-6 and Its Soluble Receptor Induce TIMP-1 Expression in Synoviocytes and Chondrocytes, and Block IL-1-induced Collagenolytic Activity

Apoptosis in the Cervix of Pregnant Rats in Association with Cervical Softening

Inhibition of connective tissue growth factor/CCN2 expression in human dermal fibroblasts by interleukin‐1α and β

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