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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of Dermatophagoides farinae (Df) and interleukin (IL)-2 on the release of eosinophil colony-stimulating factor (Eo-CSF) activity from mononuclear cells (MNC) and lymphocytes of patients with bronchial asthma (BA) who were sensitive to Df to clarify its relationship with IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF). MNC and T cells of patients cultured with IL-2 and Df released Eo-CSF activity. These Eo-CSF activities were partially inhibited by anti-IL-5 and anti-GM-CSF antibodies. In 11 of 15 cases studied, MNC from patients produced GM-CSF in response to IL-2. In four of 15 cases studied, MNC from patients produced GM-CSF in response to Df. On culture with IL-2 or Df, the releases of IL-5 into the medium by MNC from individual patients varied. The results indicate that in BA responsiveness of lymphocytes to Df is increased, and suggest that IL-5 and GM-CSF produced by T cells play a role in the induction of eosinophilia and the pathogenesis of BA.
Am J Respir Cell Mol Biol 1993 Oct
PMID:Production of interleukin-5 and granulocyte/macrophage colony-stimulating factor by T cells of patients with bronchial asthma in response to Dermatophagoides farinae and its relation to eosinophil colony-stimulating factor. 839 76

Inflammation in nasal and airway tissue caused by allergens, microbial infection, and air pollution are likely to be regulated by inflammatory mediators produced by airway epithelial cells. We have therefore investigated the baseline expression of a number of cytokine genes known to be important inducers and modulators of inflammation, in freshly isolated human nasal epithelium. Cells were obtained by superficial scraping of turbinate tissue, and cDNA for polymerase chain reaction (PCR) amplification was reverse-transcribed directly from lysates of 3 x 10(3) to 5 x 10(3) epithelial cells using random hexamers. Constitutive expression of relatively high levels of interleukin-8 (IL-8) mRNA but undetectable levels (< 1 mRNA copy/cell) of granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-6, IL-1, or tumor necrosis factor (TNF) mRNA were found after PCR amplification of the cDNA. IL-8 protein, but not IL-6, was identified in the nasal epithelial cells by immunocytochemistry. Infection with respiratory syncytial virus (RSV) or stimulation of nasal epithelium for 4 h with TNF or IL-1 in vitro resulted in a 4- to 10-fold increase in IL-8 mRNA expression but not in the expression of detectable levels of mRNA for the other cytokines. IL-8 was secreted by RSV-, IL-1-, and TNF-stimulated as well as unstimulated nasal epithelial cells after 6 to 20 h of culture. Neither IL-6, GM-CSF, nor TNF activity/immunoreactivity was detectable in the culture supernatants. Thus, it appears that IL-8 is a major cytokine of human nasal epithelium, constitutively expressed and readily secreted upon virus infection or stimulation with IL-1 and TNF.
Am J Respir Cell Mol Biol 1993 Jan
PMID:Interleukin-8 expression in normal nasal epithelium and its modulation by infection with respiratory syncytial virus and cytokines tumor necrosis factor, interleukin-1, and interleukin-6. 841 53

Interleukin-8 (IL-8) is a potent chemotactic factor for polymorphonuclear leukocytes (PMN). Here we examine whether PMN synthesize and release IL-8 in response to stimulation by selected inflammatory cytokines. PMN isolated from normal heparinized peripheral human blood were incubated in RPMI culture medium at 37 degrees C in 5% CO2, with and without granulocyte/macrophage colony-stimulating factor (GM-CSF). The culture supernatants were tested for chemotactic activity using a modified Boyden chamber. Immunoreactive IL-8 protein was measured by ELISA with a monoclonal antibody specific for IL-8. GM-CSF (0.01 to 50 ng/ml) stimulated PMN to produce chemotactic activity in a dose- and time-dependent manner. The amount of chemotactic activity reached maximal levels after 3 h of incubation with GM-CSF. Treatment of culture media supernatants with rabbit antiserum against IL-8 blocked the GM-CSF-induced chemotactic activity. IL-8 protein concentrations detected by ELISA closely paralleled the chemotactic bioactivity in both the dose-response and kinetic studies. Northern blot analysis of total RNA from PMN using a 30 mer oligonucleotide complementary to mRNA for IL-8 yielded a single 1.6-kb band. Its intensity increased 4-fold 2 h after treatment of PMN with GM-CSF. These data suggest that peripheral blood PMN can be stimulated by GM-CSF to synthesize and secrete bioactive IL-8. Since both IL-8 and GM-CSF accumulate in sites of acute inflammation, PMN may induce IL-8 gene expression in response to GM-CSF and thereby amplify the acute inflammatory response by recruiting additional PMN into inflammatory sites.
Am J Respir Cell Mol Biol 1993 Jan
PMID:Granulocyte/macrophage colony-stimulating factor stimulates human polymorphonuclear leukocytes to produce interleukin-8 in vitro. 841 54

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high-affinity human GM-CSF receptor (hGM-CSFR) in a pro-B cell line, BA/F3, by cotransfecting alpha- and beta-chain cDNA clones and showed that the reconstituted receptor could transduce growth-promoting signals. The high-affinity hGM-CSFR was also reconstituted in mouse NIH 3T3 cells, but its ability to transduce signals in fibroblasts remained undetermined. In the present study, we further characterized signal transduction by the reconstituted hGM-CSFR in both NIH 3T3 cells and BA/F3 cells. We found that the reconstituted hGM-CSFR transduces signals in NIH 3T3 fibroblasts and BA/F3 cells in response to hGM-CSF to activate transcription of the c-fos, c-jun, and c-myc proto-oncogenes. hGM-CSF also induces protein tyrosine phosphorylation and DNA synthesis in both cell types. These results indicated that hGM-CSFR is functional in fibroblasts, that signal transduction via hGM-CSFR in fibroblasts involves tyrosine kinase(s), and that association of hGM-CSFR with a factor(s) specific to hematopoietic cell lineage is not essential to transduce growth-promoting signals.
Mol Cell Biol 1993 Mar
PMID:Reconstituted human granulocyte-macrophage colony-stimulating factor receptor transduces growth-promoting signals in mouse NIH 3T3 cells: comparison with signalling in BA/F3 pro-B cells. 844 89

Fibroblasts may play an important role in the modulation of immune and inflammatory responses through elaboration of cytokines. To test this hypothesis, human lung fibroblasts were isolated from transbronchial biopsy specimens and assayed for production of interleukin-6 (IL-6) and granulocyte/macrophage colony-stimulating factor (GM-CSF). The sources of fibroblasts included lung allografts, recipient lungs obtained at time of transplant, and normal lung tissue removed during tumor resection. During the course of these studies, several early-passage fibroblasts from transplant recipients were observed to contain mycoplasma (MP)-like organisms as detected by extranuclear fluorescent staining with Hoechst 33258. Positive staining cultures were associated with isolation of Mycoplasma fermentans. IL-6 and GM-GSF as measured by ELISA were found to be elevated over 50-fold in conditioned medium from MP-infected fibroblasts as compared with noninfected lines. Treatment of cells with mycoplasma removal agent (MRA) eliminated extranuclear Hoechst fluorescence and significantly reduced the production of these cytokines. Tumor necrosis factor-beta (TNF-beta) induction of IL-6 and GM-CSF was amplified synergistically in infected cultures. No additional production of IL-6 or GM-CSF was observed in infected cultures treated with interferon-gamma (IFN-gamma) despite the ability of IFN-gamma to modestly induce IL-6 in uninfected cultures. Thus, in vitro infection of lung fibroblasts with MP represents a potent stimulus for the production of inflammatory cytokines and, therefore, necessitates rigorous control for these organisms in cell culture studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Apr
PMID:Enhanced secretion of immune-modulating cytokines by human lung fibroblasts during in vitro infection with Mycoplasma fermentans. 847 29

Activation of muscarinic acetylcholine (ACh) receptors contributes to the pathophysiological consequences of moderate experimental traumatic brain injury (TBI). Hypothermia (30 degrees C) provides protection in experimental TBI. We measured ACh levels in CSF and plasma 5 min after moderate fluid percussion TBI under normothermic or hypothermic conditions, because ACh in the CSF has been correlated with the severity of behavioral deficits after TBI. Three groups were examined: TBI with hypothermic brain (30 degrees C), TBI with normothermic brain (37 degrees C), or sham TBI with normothermic brain (37 degrees C). ACh concentrations in CSF were significantly higher in 37 degrees C TBI rats, but not in 30 degrees C TBI rats compared to shams. ACh concentrations in plasma did not differ between groups. These results suggest that a contributing factor to the neuroprotective effects of moderate hypothermia in TBI may be related to the reduction of excessive ACh levels in the central nervous system following injury.
Mol Chem Neuropathol 1993 Apr
PMID:Hypothermia blunts acetylcholine increase in CSF of traumatically brain injured rats. 850 3

Acute inhalation of the pulmonary irritant ozone is associated with an inflammatory response characterized by increased numbers of macrophages in the lung that release elevated quantities of nitric oxide. The accumulation of phagocytes in the lung is dependent on expression of leukocyte adhesion molecules including Mac-1. In the present studies, we determined whether activation of the Mac-1 receptor is involved in regulating nitric oxide production by lung phagocytes, and whether this response is modified following acute ozone inhalation. Cells were isolated from the lung by bronchoalveolar lavage 48 h after exposure of female Sprague-Dawley rats to air or ozone (2 parts per million, for 3 h). Anti-Mac-1beta antibody, but not anti-Mac-1alpha antibody, stimulated nitric oxide production by cells from both air- and ozone-exposed animals. Cells from ozone-exposed rats produced more nitric oxide and expressed greater quantities of inducible nitric oxide synthase mRNA than did cells from air-exposed animals. Production of nitric oxide in response to anti-Mac-1beta was also found to be augmented by cross-linking of the Mac-1beta receptor. Pretreatment of lavage cells with granulocyte/macrophage colony-stimulating factor (GM-CSF), which activates phagocytes, enhanced the expression of Mac-1beta and increased anti-Mac-1beta-induced nitric oxide production by the cells. Lavage cells from ozone-exposed animals were more responsive to GM-CSF than were cells from control animals. Taken together, these data suggest that the Mac-1beta adhesion molecule may contribute to phagocyte activation and mediator release during ozone-induced inflammatory reactions in the lung.
Am J Respir Cell Mol Biol 1996 Apr
PMID:Stimulation of nitric oxide production in rat lung lavage cells by anti-Mac-1beta antibody: effects of ozone inhalation. 860 Sep 36

MAP kinase (MAPK) and its activator, MAP kinase kinase (MAPKK), are commonly activated by a variety of extracellular stimuli in mammalian cells and in the process of Xenopus oocyte maturation. In order to investigate the function of the MAPK cascade in oocyte maturation, we produced an anti-Xenopus MAPKK which specifically reacts with MAPKK in vitro. When this antibody was microinjected into immature oocytes, MAPK activation induced by progesterone was prevented. Surprisingly, H1 kinase activation and germinal vesicle breakdown were also inhibited in the oocytes injected with this antibody. These results suggest that the MAPK cascade plays an important role in the maturation promoting factor (MPF) activation during the oocyte maturation process. When this antibody together with Mos was microinjected into Xenopus two-cell embryos, the Mos-induced metaphase arrest (CSF arrest) was prevented. Thus, the MAPK cascade may mediate CSF arrest. During Xenopus early embryogenesis, a low but significant level of MAPK remains active. Injection of mRNA encoding a constitutively active MAPKK resulted in mesoderm induction in animal cap explants. In addition, fibroblast growth-factor (FGF)-induced mesoderm induction was inhibited by expressing CL100 (a MAP kinase phosphatase) in animal cap explants. Thus the MAPK cascade may be involved in the mesoderm induction of Xenopus embryos. The activation pathways and roles of the MAPKK/MAPK cascade in various signaling processes will be discussed.
Mol Reprod Dev 1995 Dec
PMID:Activation mechanism and function of the MAP kinase cascade. 860 80

Reactive oxygen species (ROS) have been shown to stimulate proliferation and growth responses in a variety of mammalian cell types and to act as important mediators in many cellular processes, including hematolymphopoiesis. We examined the effect on primitive murine hematopoietic progenitor cells (HPC) of ROS generated by xanthine plus xanthine oxidase (xanthine/XO) and various antioxidants. Pretreatment of murine HPC (C57BL/6) with xanthine/XO produced a dose-dependent enhancement of clonogenic response to granulocyte/macrophage colony-stimulating factor (GM-CSF) but not to interleukin-3 or granulocyte colony-stimulating factor. Stem cell factor (SCF), a potent comitogen for many hematopoietic growth factors, also synergized with GM-CSF. However, the synergistic enhancement of GM-CSF with xanthine/XO and SCF was not additive, indicating that xanthine/XO and SCF may target the same subpopulation of HPC. Support for this conclusion came from experiments demonstrating that 1) mutant mice strains constitutively lacking a SCF-responsive population of HPC [White spotted (W/WV) and Steel (SI/SId)] are unresponsive to xanthine/XO- and SCF-induced enhancement of GM-CSF and 2) 3,4-epoxybutene, which selectively abrogates SCF synergy with GM-CSF, inhibits xanthine/XO-induced enhancement. As xanthine/XO can mimic SCF in this population of HPC, the possibility exists that ROS also play a role in normal SCF-mediated proliferation of these cells. To test this hypothesis, we used the antioxidants N-tert-butyl-alpha-phenylnitrone, exogenous superoxide dismutase, and catalase. Both N-tert-butyl-alpha-phenylnitrone and superoxide dismutase effectively inhibited SCF and xanthine/XO synergism with GM-CSF, whereas catalase had no effect, indicating that the superoxide anion may be involved. Also, none of these compounds affected SCF synergism with other hematopoietic growth factors, such as interleukin-3 or granulocyte colony-stimulating factor, suggesting a population-specific phenomenon. These findings indicate that xanthine/XO mimics SCF in stimulating a subpopulation of murine HPC to proliferate and that SCF synergy with GM-CSF in this population is sensitive to antioxidant inhibition.
Mol Pharmacol 1996 Jun
PMID:Reactive oxygen species mediate stem cell factor synergy with granulocyte/macrophage colony-stimulating factor in a subpopulation of primitive murine hematopoietic progenitor cells. 864 49

SHPTP1 (PTP1C, HCP, SHP) is an SH2 domain-containing tyrosine phosphatase expressed predominantly in hematopoietic cells. A frameshift mutation in the SHPTP1 gene causes the motheaten (me/me) mouse. These mice are essentially SHPTP1 null and display multiple hematopoietic abnormalities, most prominently hyperproliferation and inappropriate activation of granulocytes and macrophages. The me/me phenotype suggests that SHPTP1 negatively regulates macrophage proliferative pathways. Using primary bone marrow-derived macrophages from me/me mice and normal littermates, we examined the role of SHPTP1 in regulating signaling by the major macrophage mitogen colony-stimulating factor 1 (CSF-1) (also known as macrophage colony-stimulating factor). Macrophages from me/me mice hyperproliferate in response to CSF-1. In the absence of SHPTP1, the CSF-1 receptor (CSF-1R) is hyperphosphorylated upon CSF-1 stimulation, suggesting that SHPTP1 dephosphorylates the CSF-1R. At least some CSF-1R-associated proteins also are hyperactivated. SHPTP1 is associated constitutively, via its SH2 domains, with an unidentified 130-kDa phosphotyrosyl protein (P130). P130 and SHPTP1 are further tyrosyl phosphorylated upon CSF-1 stimulation. Tyrosyl-phosphorylated SHPTP1 binds to Grb2 via the Grb2 SH2 domain. Moreover, in me/me macrophages, Grb2 is associated, via its SH3 domains, with several tyrosyl phosphoproteins. These proteins are hyperphosphorylated on tyrosyl residues in me/me macrophages, suggesting that Grb2 may recruit substrates for SHPTP1. Our results indicate that SHPTP1 is a critical negative regulator of CSF-1 signaling in vivo and suggest a potential new function for Grb2.
Mol Cell Biol 1996 Jul
PMID:Regulation of colony-stimulating factor 1 receptor signaling by the SH2 domain-containing tyrosine phosphatase SHPTP1. 866 85


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