Effect of chemically modified tetracycline on transforming growth factor-β1 and caspase-3 activation in liver of septic rats*

Maitra, Soumyajit; Shapiro, Marc J.; Bhaduri, Sikha; el-Maghrabi, M R

doi:10.1097/01.ccm.0000169880.82060.f7

Cited by 19 publications

(19 citation statements)

References 25 publications

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“…47,48 Moreover, HDX could inhibit matrix metalloproteinases and AAT activities, in addition to reversing the increased AAT levels in plasma as demonstrated by a few rat experiments. [49][50][51] Furthermore, HDX could inhibit AAT activities and the generation of endogenous SO 2 in both pulmonary tissues and myocardium. 17,18,36 The present results showed that compared with vehicle-treated cells, OA induced a marked reduction of SO 2 generation but a significant increase in O 2 À and OH À generation, which could be reversed by supplementation of SO 2 .…”

Section: Discussionmentioning

confidence: 99%

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Chen

Zheng

Liu

et al. 2015

Laboratory Investigation

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The role of endogenous sulfur dioxide (SO 2 ), an efficient gasotransmitter maintaining homeostasis, in the development of acute lung injury (ALI) remains unidentified. We aimed to investigate the role of endogenous SO 2 in the pathogenesis of ALI. An oleic acid (OA)-induced ALI rat model was established. Endogenous SO 2 levels, lung injury, oxidative stress markers and apoptosis were examined. OA-induced ALI rats showed a markedly downregulated endogenous SO 2 /aspartate aminotransferase 1 (AAT1)/AAT2 pathway and severe lung injury. Chemical colorimetry assays demonstrated upregulated reactive oxygen species generation and downregulated antioxidant capacity in OA-induced ALI rats. However, SO 2 increased endogenous SO 2 levels, protected against oxidative stress and alleviated ALI. Moreover, compared with OA-treated cells, in human alveolar epithelial cells SO 2 downregulated O 2 À and OH À generation. In contrast, L-aspartic acid-b-hydroxamate (HDX, Sigma-Aldrich Corporation), an inhibitor of endogenous SO 2 generating enzyme, promoted free radical generation, upregulated poly (ADP-ribose) polymerase expression, activated caspase-3, as well as promoted cell apoptosis. Importantly, apoptosis could be inhibited by the free radical scavengers glutathione (GSH) and N-acetyl-L-cysteine (NAC). The results suggest that SO 2 /AAT1/AAT2 pathway might protect against the development of OA-induced ALI by inhibiting oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Chen

Zheng

Liu

et al. 2015

Laboratory Investigation

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“…Matrix metalloproteinases are a class of zinc-dependent enzymes that are involved in the proteolysis and re-synthesis of the ECM [8,9], processing of chemokines and cytokines to active forms [10], the release of sequestered growth and signaling factors [11] and chemotaxis and migration of leukocytes through inflamed tissues [12e14]. With regard to chlamydial infections, a role for MMP has also been proposed in trachoma [15,16] and enhanced MMP expression has been reported in an in vitro model of human fallopian tube infection [17].…”

Section: Introductionmentioning

confidence: 99%

A role for matrix metalloproteinase-9 in pathogenesis of urogenital Chlamydia muridarum infection in mice

Imtiaz

Distelhorst

Schripsema

et al. 2007

Microbes and Infection

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Matrix metalloproteinases (MMPs) are a family of host-derived enzymes involved in the turnover of extracellular matrix (ECM) molecules and the processing of cytokines, chemokines and growth factors. We have previously reported that global inhibition of MMP in Chlamydia muridarum urogenital tract infection of susceptible strains of female mice impeded ascension of C. muridarum into the upper genital tract, blunted acute inflammatory responses and reduced the rate of formation of chronic disease. Because we have also observed that MMP-9 (also known as gelatinase B) is expressed in relatively large quantities in susceptible strains of mice in response to infection during acute phases of infection, we explored this further in a more selected fashion. We infected MMP-9 gene knockout mice and wild type controls intravaginally with C. muridarum. Both groups of mice had similar isolation rates from the lower urogenital tract but the absence of MMP-9 resulted in a slightly lower isolation rate in the upper genital tract, blunted acute inflammatory indices in the affected tissues and a reduced rate of formation of hydrosalpinx-a surrogate marker of infertility. These results imply that MMP-9 is involved in pathogenesis of chlamydial infection in this model possibly by amplifying inflammatory responses.

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“…Interestingly, oxygen and nitrogen radicals have likewise been shown to have regulatory effects on host enzymes that influence the degradation of extracellular matrix (ECM) and fibrosis (13). The matrix metalloproteinases (MMP) are a class of zinc-dependent enzymes that are involved in the proteolysis and resynthesis of the ECM (18,44), processing of cytokines to active forms (19), release of sequestered growth and signaling factors (14), and chemotaxis and migration of leukocytes through inflamed tissues (17,40,41). In addition to a pivotal role in fibrosis, MMP activity has been linked to atherosclerosis (11), angiogenesis associated with tumor growth and metastasis (5), and rheumatoid arthritis and other autoimmune disorders (10).…”

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confidence: 99%

Inhibition of Matrix Metalloproteinases Protects Mice from Ascending Infection and Chronic Disease Manifestations Resulting from UrogenitalChlamydia muridarumInfection

Imtiaz¹,

Schripsema²,

Sigar³

et al. 2006

Infect Immun

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Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in the turnover of extracellular matrix molecules. We have previously reported enhanced expression of matrix metalloproteinases in Chlamydia muridarum urogenital tract infection of female mice. Kinetics and patterns of MMP expression as well as enhanced expression in susceptible strains of mice in the prior study implied a role for MMP in pathogenesis. To explore this further, we infected a susceptible strain of mice (C3H/HeN) with C. muridarum and treated two groups of mice with either one of two chemical inhibitors of MMP (MMPi; captopril and a chemically modified tetracycline) and reserved infected sham-treated mice as controls. Neither of the treatments affected shedding of viable chlamydiae from the lower urogenital tract, but the administration of either MMPi protected mice from the formation of hydrosalpinx-a surrogate marker of oviduct occlusion and infertility. Interestingly, the mechanism of protection for mice treated with chemically modified tetracycline 3, appeared to be related to prevention of ascending upper genital tract infection. These results imply that MMP are involved in pathogenesis of chlamydial infection in this model by mediating ascension of the infection into the upper genital tract. The mouse model of female urogenital tract infection withChlamydia muridarum (previously, the mouse pneumonitis strain of Chlamydia trachomatis, MoPn) has been used for over 20 years to study immunological protection related to chlamydial infections (25). More recently, it has been used to study pathological immune responses during chlamydia infection. Hydrosalpinx formation, infertility, and fibrotic oviduct occlusion are routine consequences of infection following a single urogenital inoculation of Chlamydia muridarum in susceptible mouse strains. Each of these manifestations is positively correlated with the others and also occurs in resistant strains, but at a lower rate (8,30).We have found that nitrogen and oxygen radicals interact to have a major role in influencing pathogenesis in this model (23). In the absence of phagocyte oxidase, mice are spared from the chronic sequelae of hydrosalpinx and infertility following chlamydial infection, whereas the loss of inducible nitric oxide synthase significantly increases the rate of chronic sequelae. Interestingly, oxygen and nitrogen radicals have likewise been shown to have regulatory effects on host enzymes that influence the degradation of extracellular matrix (ECM) and fibrosis (13). The matrix metalloproteinases (MMP) are a class of zinc-dependent enzymes that are involved in the proteolysis and resynthesis of the ECM (18, 44), processing of cytokines to active forms (19), release of sequestered growth and signaling factors (14), and chemotaxis and migration of leukocytes through inflamed tissues (17,40,41). In addition to a pivotal role in fibrosis, MMP activity has been linked to atherosclerosis (11), angiogenesis associated with tumor growth and metastasis (5), and rheum...

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Effect of chemically modified tetracycline on transforming growth factor-β1 and caspase-3 activation in liver of septic rats*

Abstract: Our results are consistent with an MMP-9-induced caspase-3 activation in response to CLP. CMT-3 posttreatment increased TIMP-1 level and thereby inhibited MMP-9, which in turn decreased TGF-beta1 and caspase-3 signaling pathways and improved survivability in septic rats.

Cited by 19 publications

References 25 publications

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

A role for matrix metalloproteinase-9 in pathogenesis of urogenital Chlamydia muridarum infection in mice

Inhibition of Matrix Metalloproteinases Protects Mice from Ascending Infection and Chronic Disease Manifestations Resulting from UrogenitalChlamydia muridarumInfection

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