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)

CSF have a broad range of effects on differentiated cells outside the bone marrow. Site-specific elaboration of these factors may influence local immune reactions. Keratinocytes have been demonstrated to produce a number of immunoactive cytokines, including factors capable of modifying macrophage function. We have previously identified at least two products of keratinocytes that induce DNA synthesis by elicited peritoneal macrophages; one factor has been identified as granulocyte-macrophage CSF. In the present study, the second keratinocyte product has been characterized and identified as macrophage-CSF (M-CSF). Conditioned media from cultures of normal human keratinocytes and the transformed murine keratinocyte cell line PAM 212 induce formation of macrophage colonies in soft agar as well as dose-dependent proliferation of the M-CSF-dependent cell line BAC1.2F5. The bioactivity in both assays is blocked by neutralizing anti-M-CSF antibody. Western blot analysis of cell lysates from both PAM 212 and normal human keratinocytes demonstrates multiple molecular mass forms of M-CSF (45 to 98 kDa). Northern blot analysis (PAM 212 cells) and in situ hybridization (normal keratinocytes) demonstrate expression of M-CSF mRNA. Stimulation of keratinocytes with LPS increases M-CSF synthesis as measured both by bioactivity and level of mRNA expression. Thus, both murine and human keratinocytes produce M-CSF in vitro. Furthermore, production of keratinocyte-derived M-CSF is increased by bacterial LPS. CSF production by keratinocytes may play an important role in regulating the cutaneous immune response.
 ...
PMID:Macrophage colony-stimulating factor production by murine and human keratinocytes. Enhancement by bacterial lipopolysaccharide. 217 7

Exposure of mice to midrange UV radiation (UVB) (280-320 mm) in vivo leads to suppression of the ability to induce delayed-type hypersensitivity (DTH). Systemic administration of supernatants from UVB-exposed keratinocytes (KC) similarly inhibits the ability to induce DTH and the presence of interleukin-10 (IL-10) in the supernatants has been shown to be responsible for this effect. It has been hypothesized that release of IL-10 by KC after exposure to UVB radiation in vivo may be responsible for UVB-induced inhibition of DTH and also for the inability of chronically UVB-irradiated mice to immunologically reject immunogenic UVB-induced skin tumors. To test directly whether supernatants from UVB-irradiated KC can inhibit presentation of tumor-associated antigens (TAA) by epidermal Langerhans cells (LC), cultures of the transformed murine KC line PAM 212 were exposed to 200 J/m2 of UVB radiation and 24 h supernatants obtained. CAF1 (H-2a/d) epidermal cells (EC) enriched for LC content were exposed to supernatants from irradiated (UV-SN) or mock-irradiated (MI-SN) PAM 212 cells for 3 h followed by culture for 16 h in granulocyte-macrophage colony-stimulating factor and then were pulsed with soluble TAA derived from the murine spindle cell tumor S1509a (H-2a). ECs were then washed and injected subcutaneously into naive CAF1 mice three times at weekly intervals for priming. One week after the final immunization these mice were challenged subcutaneously with live S1509a cells and tumor growth scored over time. Pretreatment of EC with UV-SN but not MI-SN inhibited the induction of effective immunity by this immunization scheme. ECs were also treated with UV-SN or MI-SN for 3 h then pulsed with TAA and injected into a hind footpad of previously immunized mice for elicitation of a DTH response. Pretreatment of EC with UV-SN but not MI-SN inhibited the ability of EC to elicit DTH. Neutralization studies with specific neutralizing antibodies to IL-10 demonstrated that the presence of IL-10 in UV-SN was responsible for the inhibition of antigen presentation both for induction and elicitation of immunity. UV-SN inhibits tumor antigen presentation by epidermal LC through the action of IL-10.
 ...
PMID:Supernatants from UVB radiation-exposed keratinocytes inhibit Langerhans cell presentation of tumor-associated antigens via IL-10 content. 764 16

The immunosuppressive peptide cyclosporin A (CyA) is an extremely effective therapy for severe recalcitrant psoriasis, although its mechanism of action is unknown. In this study, we examined the effect of CyA on keratinocyte growth and cytokine expression, and showed that CyA inhibits the growth of murine and human keratinocytes (KC) and KC cell lines. In addition, CyA inhibits the expression of cytokine genes in a dose-dependent fashion. After 2 days' incubation with 20 microM CyA, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), and interleukin 8 (IL-8) mRNA were decreased by 4-fold, 3.3-fold and 3.3-fold, respectively, in COLO-16, a keratinocyte cell line. IL-1 biological activity recovered from COLO-16 culture supernatants decreased to one-fifth of that of controls. In the murine KC cell line PAM 212, 10 microM CyA treatment for 2 days downregulated IL-1 alpha, tumour necrosis factor-alpha (TNF-alpha) and IL-1 receptor by 60%, but had no effect on the message for interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), ornithine decarboxylase and beta-actin. Cells cultured for 5 days in the presence of CyA required much lower concentrations (2 microM) to achieve the same degree of inhibition of IL-1 alpha. Similar tissue concentrations of CyA have been reported in psoriatics undergoing CyA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cyclosporin A inhibits keratinocyte cytokine gene expression. 814 71

Dendritic cells (DCs) are required for the initiation of primary immune responses. The pattern of Toll-like receptor (TLR) expression on various subsets of these cells has been shown to differ, suggestive of distinct roles in influencing immune responses. We have examined here the responses of immature DCs derived from murine bone marrow (BMDCs) to a range of TLR ligands. BMDCs cultured for 6 days in the presence of granulocyte-macrophage colony-stimulating factor were stimulated for 24 hr with ligands to TLR1-2 [Pam(3)Cys-Ser-(Lys)(4) (PAM)], TLR2-6 (macrophage-activating lipopeptide-2 (MALP-2); zymosan or peptidoglycan (PG)], TLR3 (polyinosinic-polycytidylic acid), TLR4 [lipopolysaccharide R515 (LPS)], TLR5 (flagellin), TLR7 (polyuridylic acid) and TLR9 [CpG ODN2395 (CpG)]. DC activation was monitored using membrane marker expression and analysis of culture supernatants for cytokine/chemokine release. Ligands to TLR3 and TLR7 failed to activate BMDCs. All other TLR ligands caused elevated expression of membrane markers. PAM, MALP-2 and LPS induced high-level expression of proinflammatory cytokines and chemokines. Treatment with CpG was associated with a preferential type 1 cytokine and chemokine profile. Zymosan and PG were proinflammatory but also skewed towards a type 2 pattern of cytokines and chemokines. In contrast, flagellin did not cause marked secretion by BMDCs of cytokines or chemokines. These data for BMDCs are largely consistent with the reported TLR repertoire of freshly isolated murine Langerhans cells. In addition, murine BMDCs show selective responses to TLR ligands with respect to general activation, with differentiated cytokine patterns suggestive of potential priming for divergent immune responses.
 ...
PMID:Toll-like receptor ligand activation of murine bone marrow-derived dendritic cells. 1877 83