Modulation of Proinflammatory Bacteria- and Lipid-Coupled Intracellular Signaling Pathways in a Transwell Triple Co-Culture Model by Commensal Bifidobacterium Animalis R101-8.

Autor:	Ghadimi D; Department of Microbiology and Biotechnology, Max Rubner-Institute, Hermann-Weigmann-Str 1, D-24103 Kiel, Germany., Nielsen A; Department of Microbiology and Biotechnology, Max Rubner-Institute, Hermann-Weigmann-Str 1, D-24103 Kiel, Germany., Hassan MFY; Department of Microbiology and Biotechnology, Max Rubner-Institute, Hermann-Weigmann-Str 1, D-24103 Kiel, Germany., Fölster-Holst R; Clinic of Dermatology, University Hospital Schleswig-Holstein, Schittenhelmstr. 7, D-24105 Kiel, Germany., Ebsen M; Department of Pathology, Städtisches MVZ Kiel GmbH (Kiel City Hospital), Chemnitzstr.33, 24116 Kiel, Germany., Frahm SO; Medizinisches Versorgungszentrum (MVZ), Pathology and Laboratory Medicine Dr. Rabenhorst, Prüner Gang 7, 24103 Kiel, Germany., Röcken C; Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein, Arnold-Heller-Straße 3/14, D-24105 Kiel, Germany., de Vrese M; Department of Microbiology and Biotechnology, Max Rubner-Institute, Hermann-Weigmann-Str 1, D-24103 Kiel, Germany., Heller KJ; Department of Microbiology and Biotechnology, Max Rubner-Institute, Hermann-Weigmann-Str 1, D-24103 Kiel, Germany.
Jazyk:	angličtina
Zdroj:	Anti-inflammatory & anti-allergy agents in medicinal chemistry [Antiinflamm Antiallergy Agents Med Chem] 2021; Vol. 20 (2), pp. 161-181.
DOI:	10.2174/1871523019999201029115618
Abstrakt:	Background and Aims: Following a fat-rich diet, alterations in gut microbiota contribute to enhanced gut permeability, metabolic endotoxemia, and low grade inflammation-associated metabolic disorders. To better understand whether commensal bifidobacteria influence the expression of key metaflammation-related biomarkers (chemerin, MCP-1, PEDF) and modulate the pro-inflammatory bacteria- and lipid-coupled intracellular signaling pathways, we aimed at i) investigating the influence of the establishment of microbial signaling molecules-based cell-cell contacts on the involved intercellular communication between enterocytes, immune cells, and adipocytes, and ii) assessing their inflammatory mediators' expression profiles within an inflamed adipose tissue model. Material and Methods: Bifidobacterium animalis R101-8 and Escherichia coli TG1, respectively, were added to the apical side of a triple co-culture model consisting of intestinal epithelial HT-29/B6 cell line, human monocyte-derived macrophage cells, and adipose-derived stem cell line in the absence or presence of LPS or palmitic acid. mRNA expression levels of key lipid metabolism genes HILPDA, MCP-1/CCL2, RARRES2, SCD, SFRP2 and TLR4 were determined using TaqMan qRT-PCR. Protein expression levels of cytokines (IL-1β, IL-6, and TNF-α), key metaflammation-related biomarkers including adipokines (chemerin and PEDF), chemokine (MCP- 1) as well as cellular triglycerides were assessed by cell-based ELISA, while those of p-ERK, p-JNK, p-p38, NF-κB, p-IκBα, pc-Fos, pc-Jun, and TLR4 were assessed by Western blotting. Results: B. animalis R101-8 inhibited LPS- and palmitic acid-induced protein expression of inflammatory cytokines IL-1β, IL-6, TNF-α concomitant with decreases in chemerin, MCP-1, PEDF, and cellular triglycerides, and blocked NF-kB and AP-1 activation pathway through inhibition of p- IκBα, pc-Jun, and pc-Fos phosphorylation. B. animalis R101-8 downregulated mRNA and protein levels of HILPDA, MCP-1/CCL2, RARRES2, SCD and SFRP2 and TLR4 following exposure to LPS and palmitic acid. Conclusion: B. animalis R101-8 improves biomarkers of metaflammation through at least two molecular/signaling mechanisms triggered by pro-inflammatory bacteria/lipids. First, B. animalis R101-8 modulates the coupled intracellular signaling pathways via metabolizing saturated fatty acids and reducing available bioactive palmitic acid. Second, it inhibits NF-kB's and AP-1's transcriptional activities, resulting in the reduction of pro-inflammatory markers. Thus, the molecular basis may be formed by which commensal bifidobacteria improve intrinsic cellular tolerance against excess pro-inflammatory lipids and participate in homeostatic regulation of metabolic processes in vivo. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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