Transforming growth factor β1 regulation of macrophage activation depends on the triggering stimulus

Corradin, Sally Betz; Buchmüller-Rouiller, Y; Smith, Josiane; Suardet, L.; Mauël, Jacques

doi:10.1002/jlb.54.5.423

Cited by 21 publications

(9 citation statements)

References 35 publications

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“…Böttner et al 2000;Unsicker and Strelau 2000;Schuster and Krieglstein 2002). Several earlier studies report that many members of the TGF-β superfamily are involved in inflammatory processes, such as those in arteriosclerotic lesions (Corradin et al 1993;Letterio and Roberts 1998;Bobik et al 1999;Reckless et al 2001). We here show for the first time GDF-15/MIC-1-ir cells in human arteriosclerotic carotid arteries, which have been identified as MΦ.…”

Section: Gdf-15/mic-1 Expression and Oxidative Stress In Human Mφ In mentioning

confidence: 58%

Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions

et al. 2004

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Growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) is a new member of the transforming growth factor beta (TGF-beta) superfamily, which has most recently been found in activated macrophages (MPhi). We have now investigated GDF-15/MIC-1 in human MPhi after exposure to oxidized low-density lipoproteins (oxLDL) related mediators in vitro and in arteriosclerotic carotid arteries. Using RT-PCR and Western blotting a pronounced induction of GDF-15/MIC-1 expression by oxLDL, C6-ceramide, tumor necrosis factor (TNFalpha) and hydrogen peroxide (H2O2) was found in cultured human MPhi. In 11 human arteriosclerotic carotid arteries, immunohistochemical analyses supported by computer-assisted morphometry and regression analyses demonstrated a significant colocalization of GDF-15/MIC-1 immunoreactivity (IR) with oxLDL IR and manganese superoxide dismutase (MnSOD) IR in CD68 immunoreactive (ir) MPhi, which were also expressing AIF-IR (apoptosis-inducing factor), caspase-3-IR (CPP32), PARP-IR, c-Jun/AP-1-IR and p53-IR. Our data suggest that GDF-15/MIC-1 is inducible in human MPhi by oxLDL and its mediators in vitro and is supposed to contribute to oxidative stress dependent consequences in arteriosclerotic plaques, e.g. modulating apoptosis and inflammatory processes in activated MPhi.

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Section: Gdf-15/mic-1 Expression and Oxidative Stress In Human Mφ In mentioning

confidence: 58%

Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions

et al. 2004

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“…Additionally, the level of protection corresponded with increasing amounts of TNF-␣, which is also associated with a Th1 response. Conceivably, TNF-␣ production in conjunction with IFN-␥ provides the optimal environment for macrophage activation and subsequent killing of the parasite (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

DNA Immunization with the Gene Encoding P4 Nuclease ofLeishmania amazonensisProtects Mice against Cutaneous Leishmaniasis

Campbell¹,

Diao²,

Ji³

et al. 2003

Infect Immun

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Infection with the protozoan parasite Leishmania amazonensis can cause diverse clinical forms of leishmaniasis. Immunization with purified P4 nuclease protein has been shown to elicit a protective response in mice challenged with L. amazonensis and L. pifanoi. To explore the potential of a DNA-based vaccine, we tested the L. amazonensis gene encoding P4 nuclease as well as adjuvant constructs encoding murine interleukin-12 (IL-12) and L. amazonensis HSP70. Susceptible BALB/c mice were immunized with the DNA encoding P4 alone, P4/IL-12, or P4/HSP70 prior to challenge with L. amazonensis promastigotes. Mice given P4/IL-12 exhibited no lesion development and had a 3-to 4-log reduction in tissue parasite burdens compared to controls. This protection corresponded to significant increases in gamma interferon and tumor necrosis factor alpha production and a reduction in parasite-specific immunoglobulin G1, suggesting an enhancement in Th1 responses. Moreover, we immunized mice with the L. amazonensis vaccines to determine if this vaccine regimen could provide cross-protection against a genetically diverse species, L. major. While the P4/HSP70 vaccine led to self-healing lesions, the P4/IL-12 vaccine provided negligible protection against L. major infection. This is the first report of successful use of a DNA vaccine to induce protection against L. amazonensis infection. Additionally, our results indicate that different vaccine combinations, including DNA encoding P4, HSP70, or IL-12, can provide significant protection against both Old World and New World cutaneous leishmaniasis.Leishmaniasis is widespread in over 88 countries. It is estimated that 350 million people live in areas where it is endemic, with 12 million people infected, and that approximately 1.5 million new cases occur each year (65). Current control measures rely on chemotherapy, vector control, and control of reservoir host populations. The chemotherapeutic agents used presently are inadequate, expensive, and often toxic. Due to the existing problems associated with leishmaniasis and the high incidence of infection, the World Health Organization has made it a major goal to develop an effective and affordable vaccine against leishmaniasis.The different Leishmania species cause a broad spectrum of human diseases. L. amazonensis is known to be associated with cutaneous, diffuse cutaneous, and visceral leishmaniasis in South and Central America. The pathological mechanisms responsible for the variable outcomes of infection in humans are not fully understood; however, it is generally agreed that longlasting immunity against reinfection can be developed in cutaneous leishmaniasis patients. Several vaccination trials have demonstrated that killed L. amazonensis can induce protection from natural infection (3,18,42,46,63). However, the efficacy of heat-killed vaccines against Leishmania has been extremely low (36) or highly variable within the same study (47,55). Live parasites have been used as a vaccine strategy, and although they are highly effective in indu...

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“…Moreover, IL-10 [29, 321 and TGF-P [33, 341 were shown to inhibit cytokine production. In addition, TGF-P blocks the release of activated oxygen [35] or nitrogen species [31,34,361 by activated macrophages. Indeed, IL-10 at nanogram per milliliter concentrations strongly inhibited class I1 MHC expression as well as MDHMdependent TNF-a formation (Fig.…”

Section: Neither Il-10 Nor Tgf-fi Are Responsible For Mdhm-dependent mentioning

confidence: 99%

Mycoplasma fermentans‐derived lipid inhibits class II major histocompatibility complex expression without mediation by interleukin‐6, interleukin‐10, tumor necrosis factor, transforming growth factor‐β, type I interferon, prostaglandins or nitric oxide

1996

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Mycoplasma cause several diseases in man and animals. Some strains can chronically infect humans, leading to fever or inflammatory syndromes such as arthritis, particularly in immunosuppressed patients. A set of pathogenicity factors shared by many mollicutes may be membrane components that activate macrophages to secrete cytokines and other inflammatory mediators. Mycoplasma-derived high molecular weight material (MDHM) is a macrophage-activating amphiphilic lipid which was purified from Mycoplasma fermentans. We studied the influence of MDHM on the expression of major histocompatibility complex (MHC) class II molecules by mouse resident peritoneal macrophages with an ELISA. Highly purified MDHM at 4 ng/ml and 0.8 microgram/ml crude heat-killed M. fermentans (concentrations chosen to give maximal responses) suppressed interferon (IFN)-gamma-dependent class II MHC induction when added simultaneously with IFN-gamma. MDHM was not toxic and did not result in loss of adherent cells. Kinetic data showed that MDHM first up-regulated, then down-regulated the expression of preformed class II MHC molecules, while expression of Mac-1 and F4/80 antigens remained constant. MDHM-dependent suppression of class II MHC molecule expression resulted in impaired antigen presentation to the helper T cell line D10.G4.1. We further attempted to identify hypothetical products of MDHM-stimulated macrophages as secondary mediators of class II MHC suppression such as were described for lipopolysaccharide (LPS)-stimulated macrophages. Type I IFN, prostaglandins and nitric oxide, all reported to cause down-regulation of class II MHC, could be excluded in this context. Of the cytokines tumor necrosis factor, interleukin (IL)-6, IL-10 and transforming growth factor-beta, only IL-10 inhibited class II MHC expression, although less effectively than MDHM. The involvement of IL-10 was ruled out, as no evidence for its MDHM-dependent formation could be found. Our data suggest that MDHM interferes with class II MHC expression by up-regulating its turnover, and at the same time, inhibits the formation of new class II MHC molecules.

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Transforming growth factor β1 regulation of macrophage activation depends on the triggering stimulus

Cited by 21 publications

References 35 publications

Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions

Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions

DNA Immunization with the Gene Encoding P4 Nuclease ofLeishmania amazonensisProtects Mice against Cutaneous Leishmaniasis

Mycoplasma fermentans‐derived lipid inhibits class II major histocompatibility complex expression without mediation by interleukin‐6, interleukin‐10, tumor necrosis factor, transforming growth factor‐β, type I interferon, prostaglandins or nitric oxide

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