S K Singh1, H Morbach, T Nanki, H J Girschick. 1. Pediatric Rheumatology and Infectious Diseases, Children's Hospital, University of Wuerzburg, Wuerzburg, Germany.
Abstract
OBJECTIVE: Lyme borreliosis is characterized by strong inflammatory reactions probably due to the presence of Borrelia burgdorferi in the joint. It has been suggested that Borrelia induces the immunological mechanisms that either can amplify the inflammatory response or can suppress it. To reveal the underlying mechanisms of chemoattraction and activation of responding leukocytes, we investigated the induction of chemokines in human synoviocytes exposed to two different B. burgdorferi sensu stricto isolates (strain Geho and B31). METHODS: Synoviocytes were exposed in vitro up to 5 days. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to assess the relative chemokine mRNA expression of RANTES/CCL5, SDF-1alpha/CXCL12 alpha, SDF-1beta/CXCL12 beta, MCP-1/CCL2, MCP-2/CCL8, IL-8/CXCL8 and MIP-1alpha/CCL3, and enzyme-linked immunosorbant assay (ELISA) was used to assess the protein expression of RANTES, SDF-1, MCP-1, and MIP-1alpha in the culture supernatant. RESULTS: MCP-1 gene expression was not changed by strain B31 but MCP-1 gene expression along with protein concentration was suppressed by strain Geho. Both strains induced RANTES mRNA and protein concentration. SDF-1 gene expression was suppressed, whereas protein concentrations were unchanged by both strains. IL-8 gene expression was unchanged by using strain Geho but significantly upregulated by strain B31. Both strains induced MCP-2 mRNA expression. MIP-1alpha mRNA expression was induced, but chemokine concentration was suppressed by both strains. CONCLUSION: This study suggests that the orchestra of chemokines plays an important role in the immunopathogenesis of early Lyme arthritis.
OBJECTIVE:Lyme borreliosis is characterized by strong inflammatory reactions probably due to the presence of Borrelia burgdorferi in the joint. It has been suggested that Borrelia induces the immunological mechanisms that either can amplify the inflammatory response or can suppress it. To reveal the underlying mechanisms of chemoattraction and activation of responding leukocytes, we investigated the induction of chemokines in human synoviocytes exposed to two different B. burgdorferi sensu stricto isolates (strain Geho and B31). METHODS: Synoviocytes were exposed in vitro up to 5 days. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to assess the relative chemokine mRNA expression of RANTES/CCL5, SDF-1alpha/CXCL12 alpha, SDF-1beta/CXCL12 beta, MCP-1/CCL2, MCP-2/CCL8, IL-8/CXCL8 and MIP-1alpha/CCL3, and enzyme-linked immunosorbant assay (ELISA) was used to assess the protein expression of RANTES, SDF-1, MCP-1, and MIP-1alpha in the culture supernatant. RESULTS: MCP-1 gene expression was not changed by strain B31 but MCP-1 gene expression along with protein concentration was suppressed by strain Geho. Both strains induced RANTES mRNA and protein concentration. SDF-1 gene expression was suppressed, whereas protein concentrations were unchanged by both strains. IL-8 gene expression was unchanged by using strain Geho but significantly upregulated by strain B31. Both strains induced MCP-2 mRNA expression. MIP-1alpha mRNA expression was induced, but chemokine concentration was suppressed by both strains. CONCLUSION: This study suggests that the orchestra of chemokines plays an important role in the immunopathogenesis of early Lyme arthritis.
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