PubMed · 11994402
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
David E Levy, Chien-kuo Lee. 2002. What does Stat3 do?. https://doi.org/10.1172/jci15650
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3 and STAT5, have been demonstrated in a variety of human tumours and cancer cell lines. However, data on the expression of these STATs in nasopharyngeal carcinoma (NPC) are limited. In this study, the expression patterns of STAT1, STAT3 and STAT5 were immunohistochemically examined on the archival specimens from 61 patients with NPC. Staining results of each STATs were then correlated with the clinical parameters and prognosis of these patients. The results showed that constitutive activation of STAT3 and STAT5 was detected in the majority, 70.5 and 62.3%, respectively, of the 61 tumour specimens. Furthermore, coexpression of activated STAT3 and STAT5 was found in 54.1% of the specimens. In contrast, constitutive activated STAT1 could only be detected in 8 (13.1%) cases. Surprisingly, following radiotherapy, patients with constitutive STAT5 activation, or activation of both STAT3 and STAT5, had better disease-free survival and overall survival than those without activated STAT5. To our knowledge, this is the first report providing the overall expression patterns and prognostic significance of specific STATs in NPC.
We have shown previously that the G protein-coupled production of superoxide anion (O2-) leads to closure of small-conductance Cl- channels (0.3-0.4 pS) in the basolateral membrane of rabbit parietal cells. In the present study, effects of interleukin-1beta (IL-1beta) on the Cl- channel were investigated. In the whole-cell patch-clamp recording, IL-1beta (0.3-10 ng ml-1) inhibited the whole-cell Cl- current recorded from a parietal cell within isolated rabbit gastric glands. Variance noise analysis of the whole-cell Cl- current showed that the single channel conductance of the Cl- channel that is sensitive to IL-1beta is 0.37 pS. The IL-1beta (1 ng ml-1)-induced decrease of the Cl- current was abolished by anti-IL-1beta antibody (2 microg ml-1), recombinant IL-1 receptor antagonist (500 ng ml-1), GDPbetaS (500 microM) and superoxide dismutase (100 units ml-1), a scavenger of O2-. Northern blot analysis showed that the mRNA of the IL-1 receptor was selectively expressed in rabbit gastric parietal cells. In the dihydrofluorescein diacetate-loaded single parietal cells in gastric glands, IL-1beta (0.3-10 ng ml-1) stimulated the production of oxygen radicals. Y-27632 (1-10 microM), a specific Rho-kinase inhibitor, and fluvastatin (10 microM), an indirect inhibitor for Rho proteins, significantly inhibited the IL-1beta-induced effects on the channel activity and production of oxygen radicals. IL-1beta (0.3-10 ng ml-1) activated Rho in the parietal cells. These results indicate that IL-1beta binds to the IL-1 receptor of gastric parietal cells and inhibits the small-conductance Cl- channel via the G protein-mediated Rho/Rho-kinase-dependent production of O2-.
In addition to acting as a physical barrier against microorganisms, the skin produces antimicrobial peptides and proteins. After wounding, growth factors are produced to stimulate the regeneration of tissue. The growth factor response ceases after regeneration of the tissue, when the physical barrier protecting against microbial infections is re-established. We found that the growth factors important in wound healing, insulin-like growth factor I and TGF-alpha, induce the expression of the antimicrobial peptides/polypeptides human cationic antimicrobial protein hCAP-18/LL-37, human beta-defensin 3, neutrophil gelatinase-associated lipocalin, and secretory leukocyte protease inhibitor in human keratinocytes. Both an individual and a synergistic effect of these growth factors were observed. These findings offer an explanation for the expression of these peptides/polypeptides in the skin disease psoriasis and in wound healing and define a host defense role for growth factors in wound healing.