Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NK cells migrate in response to C-C chemokines, including monocyte chemotactic protein-1 (MCP-1) and MCP-3. Increased migration was observed in IL-2-activated NK cells. It was therefore of interest to define the expression in resting and activated NK cells of the MCP-1 receptor (CCR2) for which two cDNAs (A and B) have been described. Specific oligonucleotides and reverse-transcriptase PCR revealed the presence in activated NK cells and mononuclear phagocytes of the fragments expected on the basis of the reported cDNAs. In addition, amplification with a common A/B- and an A-specific oligonucleotide yielded an unexpected, abundant, 1649-bp fragment. Sequence analysis as well as Northern blotting and RNase protection with different probes revealed that the CCR2 gene is expressed in activated NK cells and mononuclear phagocytes as a predominant long transcript (3.4 kb) consisting of CCR2B, followed by a novel sequence (X), corresponding to an intron in the genome, and by a CCR2A-specific portion. The predominant long transcript is polyadenylated and present in the cytoplasm. The augmented migratory capacity of IL-2 activated vs resting NK cells was associated with increased CCR2 transcript levels.
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PMID:IL-2-regulated expression of the monocyte chemotactic protein-1 receptor (CCR2) in human NK cells: characterization of a predominant 3.4-kilobase transcript containing CCR2B and CCR2A sequences. 905 2

Systemic sclerosis is a connective tissue disease characterized by excessive deposition of extracellular matrix in the skin as well as various internal organs. Cellular infiltrates are found in the dermis in early systemic sclerosis, which are suggested to play an important part. Recent studies suggest the involvement of monocyte chemoattractant protein-1, a C-C chemokine, in the fibrotic process. This study examines the role of monocyte chemoattractant protein-1 in the induction of dermal sclerosis in a murine model of bleomycin-induced scleroderma. Immunohistochemical analysis showed that expression of monocyte chemoattractant protein-1 in the infiltrating mononuclear cells was enhanced at 2 to 3 wk following bleomycin treatment, whereas expression of monocyte chemoattractant protein-1 in fibroblasts was detected at later stages in the sclerotic skin. Reverse transcriptase-polymerase chain reaction analysis showed that monocyte chemoattractant protein-1 mRNA expression in the lesional skin peaked at 2 to 3 wk following bleomycin treatment. Expression of CCR-2, a major receptor for monocyte chemo-attractant protein-1, was also upregulated in the lesional skin at both protein and mRNA levels following bleomycin treatment. Administration of anti-monocyte chemoattractant protein-1 neutralizing antibody together with local bleomycin treatment reduced dermal sclerosis, along with a decrease of collagen content in the skin as well as mRNA expression of type I collagen. In vitro analysis showed that stimulation with monocyte chemoattractant protein-1 (10 ng per mL) upregulated alpha1(I) collagen and decorin mRNA expression in normal dermal fibroblasts, whereas mRNA levels of fibronectin and biglycan were not altered. These data suggest that monocyte chemoattractant protein-1 and CCR-2 signaling plays an important part in the pathogenesis of bleomycin-induced scleroderma. Monocyte chemoattractant protein-1 may contribute to the induction of dermal sclerosis via its direct effect of upregulation of mRNA expression of extracellular matrix on fibroblasts, as well as indirect effect mediated by a number of cytokines released from immunocytes recruited into the lesional skin.
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PMID:Role of monocyte chemoattractant protein-1 and its receptor,CCR-2, in the pathogenesis of bleomycin-induced scleroderma. 1292 9