Endogenous anti-inflammatory substances, inter-α-inhibitor and bikunin
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Hiroshi Kobayashi
Abstract
There have been new developments in the elucidation of the biological functions of the inter-α-inhibitor (IαI) family. The anti-proteolytic activity of the IαI family originates from bikunin (also known as urinary trypsin inhibitor). Growing evidence indicates that bikunin is not just an anti-proteolytic agent, but can also be considered an anti-inflammatory agent that suppresses lipopolysaccharide (LPS)-induced cytokine synthesis. Bikunin functions to inhibit calcium influx and extracellular signal-regulated kinase (ERK) signaling via LPS receptors and/or as yet unidentified bikunin signaling receptors. By signaling via the LPS receptor, LPS increases calcium influx and yields phosphorylated ERK, which activates multiple transcription factors, such as nuclear factor κB (NF-κB) or early growth response-1 (Egr-1), which in turn promote cytokine expression. Deficits in the signaling cascades caused by free or cell-bound bikunin are predicted to down-regulate cytokine expression, render macrophages/neutrophils more inactive, and impair inflammatory processes. This brief review largely focuses on our current understanding of the apparent functions of bikunin, its ligands, the effector molecules with which it interacts, and its regulation.
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©2006 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal
- Leucine aminopeptidases: diversity in structure and function
- Endogenous anti-inflammatory substances, inter-α-inhibitor and bikunin
- Mitochondrial morphology and distribution in mammalian cells
- Heterogeneity in the cysteine protease inhibitor clitocypin gene family
- Mutations in the inter-SH2 domain of the regulatory subunit of phosphoinositide 3-kinase: effects on catalytic subunit binding and holoenzyme function
- Evaluation of Bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs
- The human malaria parasite Plasmodium falciparum expresses an atypical N-terminally extended pyrophosphokinase with specificity for thiamine
- Fes1p acts as a nucleotide exchange factor for the ribosome-associated molecular chaperone Ssb1p
- Detailed analysis of MIA protein by mutagenesis
- The role of human tissue kallikreins 7 and 8 in intracranial malignancies
- Prognostic significance of the expression of SR-A1, encoding a novel SR-related CTD-associated factor, in breast cancer
- Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines
- Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells
- Two secreted cystatins of the soft tick Ornithodoros moubata: differential expression pattern and inhibitory specificity
- Acknowledgment
- Contents Biological Chemistry Volume 387, 2006
- Author Index
- Subject Index
Artikel in diesem Heft
- Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal
- Leucine aminopeptidases: diversity in structure and function
- Endogenous anti-inflammatory substances, inter-α-inhibitor and bikunin
- Mitochondrial morphology and distribution in mammalian cells
- Heterogeneity in the cysteine protease inhibitor clitocypin gene family
- Mutations in the inter-SH2 domain of the regulatory subunit of phosphoinositide 3-kinase: effects on catalytic subunit binding and holoenzyme function
- Evaluation of Bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs
- The human malaria parasite Plasmodium falciparum expresses an atypical N-terminally extended pyrophosphokinase with specificity for thiamine
- Fes1p acts as a nucleotide exchange factor for the ribosome-associated molecular chaperone Ssb1p
- Detailed analysis of MIA protein by mutagenesis
- The role of human tissue kallikreins 7 and 8 in intracranial malignancies
- Prognostic significance of the expression of SR-A1, encoding a novel SR-related CTD-associated factor, in breast cancer
- Suppression of TNF-α production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines
- Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells
- Two secreted cystatins of the soft tick Ornithodoros moubata: differential expression pattern and inhibitory specificity
- Acknowledgment
- Contents Biological Chemistry Volume 387, 2006
- Author Index
- Subject Index