Anti-inflammatory effects of the GABA(B) receptor agonist baclofen in allergic contact dermatitis
| Autor: | Beatrice, Duthey, Anita, Hübner, Sandra, Diehl, Sandra, Boehncke, Jeannette, Pfeffer, Wolf-Henning, Boehncke |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Baclofen
Leukocytes Mononuclear/drug effects/physiology Anti-Inflammatory Agents Tumor Necrosis Factor-alpha/biosynthesis Dermatitis Allergic Contact/*drug therapy/pathology/physiopathology Protein Kinase C/metabolism Baclofen/*pharmacology In Vitro Techniques Mice Animals Humans GABA Agonists Protein Kinase C Cells Cultured GABA Agonists/pharmacology Tumor Necrosis Factor-alpha GABA-B Receptor Agonists Anti-Inflammatory Agents/*pharmacology Receptor Cross-Talk Receptors Chemokine/drug effects/physiology Mice Inbred C57BL Chemotaxis Leukocyte Disease Models Animal Dermatitis Allergic Contact Leukocytes Mononuclear Receptors Chemokine Female Chemotaxis Leukocyte/drug effects |
| Zdroj: | Experimental Dermatology, Vol. 19, No 7 (2010) pp. 661-666 |
| ISSN: | 0906-6705 |
| Popis: | The gamma amino butyric acid B (GABA(B)) receptor is a G protein-coupled receptor (GPCR) involved in synaptic transmission. Recent data indicate it to be also expressed on immune cells, along with chemokine receptors, which are also GPCRs. As GPCRs can undergo heterologous desensitization, we have examined the ability of baclofen, a GABA(B) receptor selective agonist, to interfere with the function of pro-inflammatory chemokine receptors known to be upregulated in cutaneous inflammation. In vitro, baclofen reduces chemotaxis of human peripheral blood mononuclear cells towards CCL2, CCL5, CXCL10, CXCL2 and CX3CL1 in a dose-dependant manner. Protein kinase C inhibitors calphostin C and G0 6976 could reverse this effect, pointing towards the involvement of both calcium-dependent and -independent protein kinase C in baclofen-induced inhibition of chemokine receptors. In an in vivo model of contact hypersensitivity in C57BL/6 mice, intraperitoneal injection of baclofen markedly alleviated signs of inflammation as well as recruitment of neutrophils, monocytes and lymphocytes into the skin. This study demonstrates a new role for the GABA(B) receptor in inflammation, making it a potential new therapeutic target to treat inflammatory skin diseases. |
| Databáze: | OpenAIRE |
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