TLR4 modulates inflammatory gene targets in the retina during Bacillus cereus endophthalmitis.
TLR4 modulates inflammatory gene targets in the retina during Bacillus cereus endophthalmitis.
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DOI：
10.1186/s12886-018-0764-8
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发表时间：
2018-04-16
影响因子：
2
通讯作者：
Callegan MC
中科院分区：
文献类型：
--
作者：
Coburn PS;Miller FC;LaGrow AL;Parkunan SM;Blake Randall C;Staats RL;Callegan MC
Endophthalmitis is a serious intraocular infection that frequently results in significant inflammation and vision loss. Because current therapeutics are often unsuccessful in mitigating damaging inflammation during endophthalmitis, more rational targets are needed. Toll-like receptors (TLRs) recognize specific motifs on invading pathogens and initiate the innate inflammatory response. We reported that TLR4 contributes to the robust inflammation which is a hallmark of Bacillus cereus endophthalmitis. To identify novel, targetable host inflammatory factors in this disease, we performed microarray analysis to detect TLR4-dependent changes to the retinal transcriptome during B. cereus endophthalmitis. C57BL/6 J and TLR4−/− mouse eyes were infected with B. cereus and retinas were harvested at 4 h postinfection, a time representing the earliest onset of neutrophil infiltration. Genes related to acute inflammation and inflammatory cell recruitment including CXCL1 (KC), CXCL2 (MIP2-α), CXCL10 (IP-10), CCL2 (MCP1), and CCL3 (MIP1-α)) were significantly upregulated 5-fold or greater in C57BL/6 J retinas. The immune modulator IL-6, intercellular adhesion molecule ICAM1, and the inhibitor of cytokine signal transduction SOCS3 were upregulated 25-, 11-, and 10-fold, respectively, in these retinas. LIF, which is crucial for photoreceptor cell survival, was increased 6-fold. PTGS2/COX-2, which converts arachidonic acid to prostaglandin endoperoxide H2, was upregulated 9-fold. PTX3, typically produced in response to TLR engagement, was induced 15-fold. None of the aforementioned genes were upregulated in TLR4−/− retinas following B. cereus infection. Our results have identified a cohort of mediators driven by TLR4 that may be important in regulating pro-inflammatory and protective pathways in the retina in response to B. cereus intraocular infection. This supports the prospect that blocking the activation of TLR-based pathways might serve as alternative targets for Gram-positive and Gram-negative endophthalmitis therapies in general. The online version of this article (10.1186/s12886-018-0764-8) contains supplementary material, which is available to authorized users.
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影响因子：
4.1
作者：
DAVID, DB;KIRKBY, GR;NOBLE, BA
通讯作者：
NOBLE, BA
DOI：
10.1152/ajplung.00109.2014
发表时间：
2016-04-01
影响因子：
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通讯作者：
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DOI：
10.1097/01.asn.0000040595.35207.62
发表时间：
2003-01-01
影响因子：
13.6
作者：
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通讯作者：
Steadman, R
影响因子：
3.1
作者：
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通讯作者：
Lereclus, D