Docampo María José, Cabrera Jennifer, Bassols Anna
Departament de Bioquímica i Biologia Molecular, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Departament de Bioquímica i Biologia Molecular, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Vet Immunol Immunopathol. 2017 Feb;184:8-17. doi: 10.1016/j.vetimm.2016.12.008. Epub 2016 Dec 23.
Hyaluronan (HA), a major component of the extracellular matrix (ECM), has been increasingly recognized as a regulator of inflammation. Its role is complex since it has pro- and anti-inflammatory actions by modulating the expression of inflammatory genes, the recruitment of inflammatory cells and the production of inflammatory cytokines, but also by attenuating the course of inflammation and providing protection against tissue damage. Certain viruses and other inflammatory stimuli induce organization of HA into cable-like structures, which may be responsible for leukocyte recruitment and, on the other hand, low molecular weight fragments of HA have been shown to activate various inflammatory responses. The aim of the present study was to analyze the effects of a simulated infection with the viral mimetic Poly (I:C) on HA deposition on different porcine intestinal cells (primary colonic muscular smooth muscle cells (SMC), and epithelial IPEC-J2 and IPI-2I cell lines) and on the recruitment of peripheral blood mononuclear cells (PBMC) to intestinal cell layers. We show that Poly (I:C) treatment induces the formation of an HA-based pericellular matrix coat in muscular SMC and in intestinal epithelial cells (IECs) and that, on differentiated IPEC-J2 cells, HA accumulates in the basolateral membrane. Porcine PBMCs bind to Poly (I:C)-treated cells and this binding is dependent on HA, since the increase in adhesion is abolished by hyaluronidase treatment of the cell layers. A second goal was to study the effect of different molecular weight HA forms on the production of pro-inflammatory cytokines and chemokines (TNF-α, IL-1β and IL-8) by porcine PBMCs. Low molecular weight HA fragments (100-150kDa), in contrast to high molecular weight HA (2500kDa), stimulate the release of these pro-inflammatory mediators by porcine PBMCs. Our results suggest that HA is involved in the inflammatory response against pathogenic insults to the porcine gut.
透明质酸（HA）是细胞外基质（ECM）的主要成分，越来越被认为是炎症的调节因子。其作用复杂，因为它通过调节炎症基因的表达、炎症细胞的募集和炎症细胞因子的产生，以及通过减轻炎症进程和提供组织损伤保护，具有促炎和抗炎作用。某些病毒和其他炎症刺激会诱导HA形成索状结构，这可能与白细胞募集有关，另一方面，已证明低分子量的HA片段可激活各种炎症反应。本研究的目的是分析用病毒模拟物聚肌苷酸-聚胞苷酸（Poly (I:C)）进行模拟感染对不同猪肠道细胞（原代结肠肌层平滑肌细胞（SMC）以及上皮IPEC-J2和IPI-2I细胞系）上HA沉积的影响，以及对外周血单核细胞（PBMC）向肠道细胞层募集的影响。我们发现，Poly (I:C)处理可诱导在肌层SMC和肠道上皮细胞（IEC）中形成基于HA的细胞周基质涂层，并且在分化的IPEC-J2细胞上，HA在基底外侧膜中积累。猪PBMC与经Poly (I:C)处理的细胞结合，这种结合依赖于HA，因为用透明质酸酶处理细胞层后，黏附增加被消除。第二个目标是研究不同分子量HA形式对猪PBMC产生促炎细胞因子和趋化因子（TNF-α、IL-1β和IL-8）的影响。与高分子量HA（2500kDa）相比，低分子量HA片段（100 - 150kDa）刺激猪PBMC释放这些促炎介质。我们的结果表明，HA参与了针对猪肠道致病性损伤的炎症反应。
