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Pattern of proinflammatory cytokine induction in RAW264.7 mouse macrophages is identical for virulent and attenuated Borrelia burgdorferi.

ABSTRACT: Lyme disease pathogenesis results from a complex interaction between Borrelia burgdorferi and the host immune system. The intensity and nature of the inflammatory response of host immune cells to B. burgdorferi may be a determining factor in disease progression. Gene array analysis was used to examine the expression of genes encoding cytokines, chemokines, and related factors in the joint tissue of infected C3H/HeJ mice and in a murine macrophage-like cell line in response to a disseminating or attenuated clinical isolate of B. burgdorferi. Both isolates elicited a robust proinflammatory response in RAW264.7 cells characterized by an increase in transcript levels of genes encoding CC and CXC chemokines, proinflammatory cytokines, and TNF superfamily members. Transcription of genes encoding IL-1beta, IL-6, MCP-1, MIP-1alpha, CXCR4, and TLR2 induced in RAW264.7 cells by either live or heat-killed spirochetes did not differ significantly at any time point over a 24-h period, nor was there a difference in the protein levels of IL-10, TNF-alpha, IL-6, and IL-12p70 in culture supernatants. Thus, induction of host macrophage expression of proinflammatory mediators by host macrophages does not contribute to the differential pathogenicity of different B. burgdorferi strains.

SUBMITTER: Wang G

PROVIDER: S-EPMC2614377 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Pattern of proinflammatory cytokine induction in RAW264.7 mouse macrophages is identical for virulent and attenuated Borrelia burgdorferi.

Wang Guiqing G Petzke Mary M MM Iyer Radha R Wu Hongyan H Schwartz Ira I

Journal of immunology (Baltimore, Md. : 1950) 20080601 12

Lyme disease pathogenesis results from a complex interaction between Borrelia burgdorferi and the host immune system. The intensity and nature of the inflammatory response of host immune cells to B. burgdorferi may be a determining factor in disease progression. Gene array analysis was used to examine the expression of genes encoding cytokines, chemokines, and related factors in the joint tissue of infected C3H/HeJ mice and in a murine macrophage-like cell line in response to a disseminating or ...[more]

PMID: 18523297

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Project description:BackgroundAlpha-momorcharin (α-MMC) is a natural medicine derived from bitter melon and has been found to exert immunomodulatory effects. Our previous study indicated that α-MMC can regulate cytokine release from monocytes, but it remains unknown about its regulatory effect on different types of cytokines, such as inflammatory cytokines or anti-inflammatory cytokines.MethodsLPS-induced M1-type macrophages model and IL-4-induced M2-type macrophages model were established, and the expression of proinflammatory cytokines and anti-inflammatory cytokines were assessed by ELISA after α-MMC was administered. Then, a LPS-induced acute pneumonia mouse model was established, the proinflammatory cytokines levels and inflammatory lesions in lung tissues were examined by ELISA or H&E staining. Furthermore, omics screening analysis and Western blotting verification were performed on TLR4 and JAK1-STAT6 signalling pathway-related proteins to elucidate the regulatory mechanism of α-MMC in those M1 macrophages and M2 macrophages.ResultsAt a noncytotoxic dose of 0.3 μg/mL, α-MMC significantly inhibited the LPS-induced expression of inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8, MIP-1α and MCP-1, by M1 macrophages in a time-dependent manner, but α-MMC did not inhibit the IL-4-induced synthesis of anti-inflammatory cytokines, such as IL-10, IL-1RA, EGF, VEGF, TGF-β and CCL22, by M2 macrophages. Moreover, α-MMC also inhibited inflammatory cytokine expression in an LPS-induced acute pneumonia mouse model and alleviated inflammation in lung tissues. Furthermore, omics screening and Western blotting analysis confirmed that α-MMC inhibited TAK1/p-TAK1 and subsequently blocked the downstream MAPK and NF-κB pathways, thus inhibiting the LPS-induced inflammatory cytokine expression.ConclusionOur results reveal that α-MMC inhibits proinflammatory cytokine expression by M1 macrophages but not anti-inflammatory cytokine expression by M2 macrophages. The efficacy of α-MMC in selectively inhibiting proinflammatory cytokine expression renders it particularly suitable for the treatment of severe inflammation and autoimmune diseases characterized by cytokine storms.

Project description:Borrelia burgdorferi and Borrelia miyamotoi are tick-vectored zoonotic pathogens maintained in wildlife species. Tick populations are establishing in new areas globally in response to climate change and other factors. New Brunswick is a Canadian maritime province at the advancing front of tick population establishment and has seen increasing numbers of ticks carrying B. burgdorferi, and more recently B. miyamotoi. Further, it is part of a region of Atlantic Canada with wildlife species composition differing from much of continental North America and little information exists as to the presence and frequency of infection of Borrelia spp. in wildlife in this region. We used a citizen science approach to collect a wide range of animals including migratory birds, medium-sized mammals, and small mammals. In total we tested 339 animals representing 20 species for the presence of B. burgdorferi and B. miyamotoi. We have developed new nested PCR primers and a protocol with excellent specificity for detecting both of these Borrelia species, both single and double infections, in tissues and organs of various wildlife species. The positive animals were primarily small non-migratory mammals, approximately twice as many were infected with B. burgdorferi than B. miyamotoi and one animal was found infected with both. In addition to established reservoir species, the jumping mouse (Napaeozapus insignis) was found frequently infected; this species had the highest infection prevalence for both B. burgdorferi and B. miyamotoi and has not previously been identified as an important carrier for either Borrelia species. Comprehensive testing of tissues found that all instances of B. burgdorferi infection were limited to one tissue within the host, whereas two of the five B. miyamotoi infections were diffuse and found in multiple systems. In the one coinfected specimen, two fetuses were also recovered and found infected with B. miyamotoi. This presumptive transplacental transmission suggests that vertical transmission in mammals is possible. This finding implies that B. miyamotoi could rapidly spread into wildlife populations, as well as having potential human health implications.

Dataset Information

Pattern of proinflammatory cytokine induction in RAW264.7 mouse macrophages is identical for virulent and attenuated Borrelia burgdorferi.

Publications

Pattern of proinflammatory cytokine induction in RAW264.7 mouse macrophages is identical for virulent and attenuated Borrelia burgdorferi.

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