Molecular mechanism for activation and regulation of matrix metalloproteinases during bacterial infections and respiratory inflammation
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Tatsuya Okamoto
Abstract
Matrix metalloproteinases (MMPs) are critical mediators of tissue remodeling. Inappropriate regulation of MMPs causes many pathological events, including microbial invasion and inflammatory tissue damage. Some of the bacterial exoproteinases can effectively activate pro-MMPs (inactive zymogens) via limited proteolysis around their autoinhibitory domains. In addition, overproduction of nitric oxide (NO) may contribute to respiratory inflammation via the formation of reactive nitrogen species (RNS). Several studies have identified regulatory properties of NO/RNS on biomolecules due to functional modification of their cysteine residues. In fact, NO/RNS can mediate activation and expression of MMPs, because RNS can interact with a cysteine switch in the autoinhibitory domain, thus converting proMMPs into their active forms without proteolysis. Many studies have indicated that NO/RNS can participate in expression of various genes that affect immune-inflammatory responses, including MMPs. Although NO in some cases upregulates MMPs, S-nitrosothiols downregulate MMP-9 expression by suppressing the NF-κB pathway. While microbial proteinases cause excessive activation of MMPs and contribute to microbial pathogenesis, NO/RNS may modulate expression and activation of MMPs as well as various inflammatory mediators, depending on the redox status at sites of inflammation. Therefore, appropriate regulation of MMPs may be of potential therapeutic value for various infections and inflammatory lung diseases.
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© Walter de Gruyter
Articles in the same Issue
- Hiroshi Maeda – 40 years of research
- Activation of the kallikrein-kinin system and release of new kinins through alternative cleavage of kininogens by microbial and human cell proteinases
- Molecular mechanism for activation and regulation of matrix metalloproteinases during bacterial infections and respiratory inflammation
- Role of bacterial proteases in pseudomonal and serratial keratitis
- Cysteine cathepsins in human cancer
- Secretory leukoprotease inhibitor and pulmonary surfactant serve as principal defenses against influenza A virus infection in the airway and chemical agents up-regulating their levels may have therapeutic potential
- Design of inhibitors against HIV, HTLV-I, and Plasmodium falciparum aspartic proteases
- Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas gingivalis: identification of its responsible molecules in translation products of rgpA, kgp, and hagA genes
- Coordinate expression of the Porphyromonas gingivalis lysine-specific gingipain proteinase, Kgp, arginine-specific gingipain proteinase, RgpA, and the heme/hemoglobin receptor, HmuR
- Genetic characterization of staphopain genes in Staphylococcus aureus
- Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin following trauma and in dermal diseases
- Reduction of myocardial infarction by calpain inhibitors A-705239 and A-705253 in isolated perfused rabbit hearts
- A proteinase inhibitor from Caesalpinia echinata (pau-brasil) seeds for plasma kallikrein, plasmin and factor XIIa
- Plasma prekallikrein/kallikrein processing by lysosomal cysteine proteases
- Characteristics of the caspase-like catalytic domain of human paracaspase
- mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment with carboplatin and doxorubicin
- Thermoplasma acidophilum TAA43 is an archaeal member of the eukaryotic meiotic branch of AAA ATPases
- Lipopolysaccharide binding of an exchangeable apolipoprotein, apolipophorin III, from Galleria mellonella
Articles in the same Issue
- Hiroshi Maeda – 40 years of research
- Activation of the kallikrein-kinin system and release of new kinins through alternative cleavage of kininogens by microbial and human cell proteinases
- Molecular mechanism for activation and regulation of matrix metalloproteinases during bacterial infections and respiratory inflammation
- Role of bacterial proteases in pseudomonal and serratial keratitis
- Cysteine cathepsins in human cancer
- Secretory leukoprotease inhibitor and pulmonary surfactant serve as principal defenses against influenza A virus infection in the airway and chemical agents up-regulating their levels may have therapeutic potential
- Design of inhibitors against HIV, HTLV-I, and Plasmodium falciparum aspartic proteases
- Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas gingivalis: identification of its responsible molecules in translation products of rgpA, kgp, and hagA genes
- Coordinate expression of the Porphyromonas gingivalis lysine-specific gingipain proteinase, Kgp, arginine-specific gingipain proteinase, RgpA, and the heme/hemoglobin receptor, HmuR
- Genetic characterization of staphopain genes in Staphylococcus aureus
- Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin following trauma and in dermal diseases
- Reduction of myocardial infarction by calpain inhibitors A-705239 and A-705253 in isolated perfused rabbit hearts
- A proteinase inhibitor from Caesalpinia echinata (pau-brasil) seeds for plasma kallikrein, plasmin and factor XIIa
- Plasma prekallikrein/kallikrein processing by lysosomal cysteine proteases
- Characteristics of the caspase-like catalytic domain of human paracaspase
- mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment with carboplatin and doxorubicin
- Thermoplasma acidophilum TAA43 is an archaeal member of the eukaryotic meiotic branch of AAA ATPases
- Lipopolysaccharide binding of an exchangeable apolipoprotein, apolipophorin III, from Galleria mellonella