Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The LFA-1 adhesion molecule is involved in cell adhesion events of leukocytes through binding to ICAM-1, ICAM-2 and ICAM-3. Whether binding to either of these ligands similarly affects co-stimulation of T cells and cytokine secretion is unknown. We demonstrated that LFA-1 co-stimulation under suboptimal concentrations of anti-CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respectively, which correlates with the distinct affinities of LFA-1 for these ligands. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted in high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interestingly, we observed that LFA-1/ICAM-1 co-stimulation of T cells resulted in high production of the Th2 cytokine IL-10 compared to ICAM-2 or ICAM-3 co-stimulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretion of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimulation, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA-1 serves as a potent co-stimulatory molecule by inducing different cytokine patterns depending on the ligand bound.
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PMID:Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3. 1042 88

We investigated the intracellular signaling mechanisms for cytokine interleukin (IL)-3, IL-5, or granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced expression of adhesion molecules including very late antigen 4 (CD49 d), macrophage antigen-1 (CD11b), leukocyte function-associated antigen-1 (CD11a/CD18), intercellular adhesion molecule (ICAM)-1, and ICAM-3 on eosinophils. The expression of adhesion molecules and nuclear factor (NF)-kappaB pathway was measured by flow cytometry and cDNA expression array, respectively. The phosphorylation of inhibitor kappaB-alpha and p38 mitogen-activated protein kinase (MAPK) was detected by Western blot, whereas NF-kappaB activity was measured by electrophoretic mobility shift assay. IL-3, IL-5, and GM-CSF could enhance p38 MAPK and NF-kappaB activity and induce ICAM-1, CD11b, and CD18 expressions on eosinophils. They could suppress ICAM-3 expression, but had no effect on CD49 d expression. Either SB 203580 or MG-132 was able to offset the cytokine-induced expression of ICAM-1. Only SB 203580 could reverse the effect on CD11b, CD18, and ICAM-3 expressions. Therefore, the expression of ICAM-1 might involve both p38 MAPK and NF-kappaB activities, whereas the regulation of CD11b, CD18, and ICAM-3 expressions might be mediated through p38 MAPK but not NF-kappaB. These cytokines therefore play a crucial role, via the p38 MAPK and NF-kappaB pathways, in the expression of important adhesion molecules on eosinophils in allergic inflammation.
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PMID:Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor-induced adhesion molecule expression on eosinophils by p38 mitogen-activated protein kinase and nuclear factor-[kappa] B. 1260 Aug 15

Exposure of human skin to solar ultraviolet (UV) light induces local and systemic immune suppression. It is known that alterations of immune functions of Langerhans cells (LCs) and dermal dendritic cells (DDCs) mediate this phenomenon. The purpose of this study was to mimic in vitro the early UV-induced skin disruption to better understand the involvement of the skin micro-environment in triggering this immunosuppressive state. We therefore developed skin equivalents (SEs) integrating LCs and DDCs derived from monocytes (mo-LCs and mo-DDCs, respectively). First, we showed that Langerin(+) mo-LC and dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (SIGN)(+) mo-DDCs were immunolocalized in situ in epidermal and dermal compartments of SEs, respectively. The SE micro-environment without immune cells displayed full cytokine profile that may ensure and maintain differentiation, localization, and immaturity of LCs and DDCs in situ, as shown by secretion of granulocyte-macrophage colony-stimulating factor, transforming growth factor beta (beta)-1, interleukin (IL)-4, IL-13, and IL-15 involved in cell differentiation; presence of complete chemokine network as macrophage inflammatory protein 3 alpha (alpha); low secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, and IL-8; and surprising secretion of immunosuppresive cytokine IL-10. Second, we demonstrated that skin micro-environment homeostasis was greatly disrupted under solar UV irradiation of SEs. In fact, we showed a pro-inflammatory state characterized by high secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 and low secretion of IL-10. This breakdown of immune homeostasis was visualized at the same time as in situ migration of mo-LCs and mo-DDCs into the dermal equivalent of SEs. Moreover, this tissue migration of mo-LCs and mo-DDCs into SEs was in accordance with the chemokine (C-C motif) receptor 7 expression and the DC-lysosome-associated membrane glycoprotein acquisition only on mo-LCs. Our results highlighted major participation of the skin micro-environment in the triggering and modulating of UV-induced skin immune responses. In addition, it could be concluded that these SEs are reliable tools for modeling biological events inaccessible in humans.
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PMID:Effects of solar ultraviolet radiation on engineered human skin equivalent containing both Langerhans cells and dermal dendritic cells. 1788 23