Merck
  • Home
  • Search Results
  • MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi.

MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi.

PLoS pathogens (2014-06-27)
Robert B Lochhead, Ying Ma, James F Zachary, David Baltimore, Jimmy L Zhao, John H Weis, Ryan M O'Connell, Janis J Weis
ABSTRACT

MicroRNAs have been shown to be important regulators of inflammatory and immune responses and are implicated in several immune disorders including systemic lupus erythematosus and rheumatoid arthritis, but their role in Lyme borreliosis remains unknown. We performed a microarray screen for expression of miRNAs in joint tissue from three mouse strains infected with Borrelia burgdorferi. This screen identified upregulation of miR-146a, a key negative regulator of NF-κB signaling, in all three strains, suggesting it plays an important role in the in vivo response to B. burgdorferi. Infection of B6 miR-146a-/- mice with B. burgdorferi revealed a critical nonredundant role of miR-146a in modulating Lyme arthritis without compromising host immune response or heart inflammation. The impact of miR-146a was specifically localized to the joint, and did not impact lesion development or inflammation in the heart. Furthermore, B6 miR-146a-/- mice had elevated levels of NF-κB-regulated products in joint tissue and serum late in infection. Flow cytometry analysis of various lineages isolated from infected joint tissue of mice showed that myeloid cell infiltration was significantly greater in B6 miR-146a-/- mice, compared to B6, during B. burgdorferi infection. Using bone marrow-derived macrophages, we found that TRAF6, a known target of miR-146a involved in NF-κB activation, was dysregulated in resting and B. burgdorferi-stimulated B6 miR-146a-/- macrophages, and corresponded to elevated IL-1β, IL-6 and CXCL1 production. This dysregulated protein production was also observed in macrophages treated with IL-10 prior to B. burgdorferi stimulation. Peritoneal macrophages from B6 miR-146a-/- mice also showed enhanced phagocytosis of B. burgdorferi. Together, these data show that miR-146a-mediated regulation of TRAF6 and NF-κB, and downstream targets such as IL-1β, IL-6 and CXCL1, are critical for modulation of Lyme arthritis during chronic infection with B. burgdorferi.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
氯仿, contains 100-200 ppm amylenes as stabilizer, ≥99.5%
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
氯仿, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
氯仿, suitable for HPLC, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
氯仿, anhydrous, contains amylenes as stabilizer, ≥99%
Sigma-Aldrich
氯仿, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains amylenes as stabilizer
Sigma-Aldrich
氯仿, contains ethanol as stabilizer, ACS reagent, ≥99.8%
Sigma-Aldrich
氯仿, puriss. p.a., reag. ISO, reag. Ph. Eur., 99.0-99.4% (GC)
Sigma-Aldrich
氯仿, suitable for HPLC, ≥99.8%, amylene stabilized
Sigma-Aldrich
氯仿, contains amylenes as stabilizer, ACS reagent, ≥99.8%
Sigma-Aldrich
7-氨基放线菌素D, ~97% (HPLC), powder
Sigma-Aldrich
氯仿, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
氯仿, contains ethanol as stabilizer, meets analytical specification of BP, 99-99.4% (GC)
Sigma-Aldrich
氯仿, ACS spectrophotometric grade, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Supelco
氯仿, analytical standard
Sigma-Aldrich
氯仿, ReagentPlus®, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Supelco
氯仿, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
氯仿, biotech. grade, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
氯仿, ≥99%, PCR Reagent, contains amylenes as stabilizer
Supelco
氯仿, suitable for HPLC, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Supelco
氯仿, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
氯仿, ACS reagent, ≥99.8%, contains amylenes as stabilizer
Sigma-Aldrich
Anti-STAT1 antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-IRAK1 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-TRAF6 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
抗-STAT1 (Ab-701) 兔抗, affinity isolated antibody
Sigma-Aldrich
Anti-TRAF6 antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-TRAF6 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab1
Sigma-Aldrich
Anti-STAT1 (AB2) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-STAT1 (AB3) antibody produced in rabbit, affinity isolated antibody