Suppression of metalloproteinase biosynthesis in human alveolar macrophages by interleukin-4.

Abstract

To study the interaction of lymphocytes and macrophages in the control of extracellular matrix turnover, we determined the effects ofseveral soluble T cell products on mononuclear phagocyte production of metalloproteinases. Cytokines including IL-2, IL4, IL-6, tumor necrosis factor a (TNFa), GM-CSF, and IFN-gamma were each tested for capacity to modulate macrophage metalloproteinase and tissue inhibitor of metalloproteinases (TIMP) expression. The addition of IL4 to cells cultured under basal conditions caused a dose-dependent suppression in the release of 92-kD type IV collagenase without affecting TIMP production. 92-kD enzyme secretion was inhibited by 50% with 1-2 ng/ ml of IL4 and by 90% with 10 ng/ml of IL4. When cells were first exposed to killed Staphylococcus aureus to induce metalloproteinase production, IL4 potently blocked the stimulated release of both interstitial collagenase and 92-kD type IV collagenase, again without effect upon TIMP. Metabolic labeling experiments and Northern hybridizations demonstrated that IL4 exerted its action at a pretranslational level. Furthermore, IL4 possessed the capacity to inhibit metalloproteinase expression even in the relatively immature peripheral blood monocyte. As reported previously

1α,25‐dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection

“…14 Our experiments confirm this previous observation in MN and show for the first time that 1a,25(OH) 2 D 3 also regulates MMP-7 and MMP-10 expression in MN under basal conditions and/or during M. tuberculosis infection. As previous studies have suggested that an interaction between T cells and MN/macrophages enhances MMP expression by both cell populations 11,[22][23][24][25] we also investigated the effects of 1a,25(OH) 2 D 3 on MMP regulation in a mixed population of adherent and non-adherent PBMC. Our observation that each MMP analysed had higher constitutive expression in PBMC than in MN led us to investigate the influence of 1a,25(OH) 2 D 3 and M. tuberculosis on MMP secretion and activity in PBMC.…”

IL-10 signaling via IL-10E1 is dependent on tyrosine phosphorylation in the IL-10R α chain in human primary prostate cancer cell lines

“…In addition, it is important to examine whether the IL-10R in human prostate tumors also binds specific STAT proteins (i.e. Studies by other laboratories have previously implicated IL-10 and other cytokines in the regulation of TIMP-1 and MMP expression in a variety of white blood cell lines (Lacraz et al, 1993(Lacraz et al, , 1995. For example, studies examining the role of IL-6 on collagenase and TIMP-1 production in human fibroblasts, synoviocytes, chondrocytes, and macrophages (Lacraz et al, 1993) indicated that IL-6 does not stimulate collagenase production, but is a potent inducer of TIMP-1.…”

“…Studies by other laboratories have previously implicated IL-10 and other cytokines in the regulation of TIMP-1 and MMP expression in a variety of white blood cell lines (Lacraz et al, 1993(Lacraz et al, , 1995. For example, studies examining the role of IL-6 on collagenase and TIMP-1 production in human fibroblasts, synoviocytes, chondrocytes, and macrophages (Lacraz et al, 1993) indicated that IL-6 does not stimulate collagenase production, but is a potent inducer of TIMP-1. In comparison, IL-4 and IFNg were found to inhibit collagenase expression, but not influence TIMP secretion (Lacraz et al, 1993).…”

“…For example, studies examining the role of IL-6 on collagenase and TIMP-1 production in human fibroblasts, synoviocytes, chondrocytes, and macrophages (Lacraz et al, 1993) indicated that IL-6 does not stimulate collagenase production, but is a potent inducer of TIMP-1. In comparison, IL-4 and IFNg were found to inhibit collagenase expression, but not influence TIMP secretion (Lacraz et al, 1993). Lacraz et al (1995) further compared the effects of IL-10, IL-4, IL-2, IL-6, and INFg on MMP-9, interstitial collagenase, and TIMP-1 synthesis in human macrophages and monocytes.…”

A novel IL-10 signalling mechanism regulates TIMP-1 expression in human prostate tumour cells

“…For example, IL-6 stimulated TIMP-1 synthesis, but had no effect on MMP synthesis (Lacraz et al, 1993(Lacraz et al, , 1995; TGF b simultaneously increased TIMP-1 mRNA levels while decreasing MMP-2 mRNA content in fibroblasts (Overall et al, 1989); and steroids suppressed the expression of MMPs while simultaneously stimulating TIMP-1 production in uterine cervical fibroblasts (Sato et al, 1991). Similarly, interleukin-1 and TNF a were found to stimulate TIMP-1 production while up regulating MMP synthesis in cultured chondrocytes (Chua and Chua, 1990;Lotz and Guerne, 1991;Martel-Pelletier et al, 1991).…”