PMID- 31629100 OWN - NLM STAT- MEDLINE DCOM- 20210726 LR - 20221207 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 126 DP - 2020 Feb TI - Candida albicans SC5314 inhibits NLRP3/NLRP6 inflammasome expression and dampens human intestinal barrier activity in Caco-2 cell monolayer model. PG - 154882 LID - S1043-4666(19)30311-4 [pii] LID - 10.1016/j.cyto.2019.154882 [doi] AB - Candida albicans is an opportunistic fungal pathogen that colonizes human gastro-intestinal mucosal tissues. Its effect on the immune response in intestinal epithelial cells and on the intestinal mucosal barrier are not yet fully understood. In this study, we investigated Caco-2 cells, a monolayer model of intestinal epithelial cells, with or without treatment with C. albicans SC5314 (CA) or heat-inactivated CA (CA-inact). RNA sequencing was conducted, and the mRNA and protein levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) or NLRP6/ASC/caspase-1 inflammasome signaling pathway components, inflammatory cytokines (interleukin-18 [IL-18] and IL-1beta), anti-microbial peptides (AMPs; beta-defensin-2 [BD-2], BD-3, and LL-37), and tight junction proteins (occludin and zona occludens-1 [ZO-1]) were examined by real-time PCR, western blotting, and/or immunofluorescence microscopy. Lactase dehydrogenase (LDH) activity in the Caco-2 cell supernatant were measured by enzyme kinetics analysis. Our results showed that the NOD-like receptor signaling pathway participates in the CA- and CA-inact-infected Caco-2 cells, as shown by microarray analysis of total mRNA expression. The expression of NLRP3, NLRP6, ASC, BD-2, BD-3, occludin, and ZO-1 were significantly decreased in Caco-2 cells infected with CA and CA-inact compared to that in the untreated control. IL-1beta expression was decreased in the Caco-2 cells in both the CA- and CA-inact-infected groups compared to that in the control. Caspase-1 and IL-18 levels were not markedly affected by CA or CA-inact in Caco-2 cells. Our findings indicate that CA can inhibit the NLRP3 and NLRP6 pathways and dampen human intestinal mucosal barrier activity by decreasing the production of AMPs and tight junction proteins, independent of CA activity. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Mao, Xiaqiong AU - Mao X AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Qiu, Xinyun AU - Qiu X AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Jiao, Chunhua AU - Jiao C AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Lu, Meijiao AU - Lu M AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhao, Xiaojing AU - Zhao X AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Li, Xueting AU - Li X AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Li, Jiajia AU - Li J AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Ma, Jingjing AU - Ma J AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhang, Hongjie AU - Zhang H AD - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: hjzhang06@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191016 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (DEFB4A protein, human) RN - 0 (IL18 protein, human) RN - 0 (IL1B protein, human) RN - 0 (Inflammasomes) RN - 0 (Interleukin-18) RN - 0 (Interleukin-1beta) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLRP3 protein, human) RN - 0 (NLRP6 protein, human) RN - 0 (Occludin) RN - 0 (TJP1 protein, human) RN - 0 (Tight Junction Proteins) RN - 0 (Zonula Occludens-1 Protein) RN - 0 (beta-Defensins) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - 0 (Cathelicidins) SB - IM MH - Antimicrobial Cationic Peptides/genetics/metabolism MH - Caco-2 Cells MH - Candida albicans/*metabolism MH - Candidiasis/enzymology/genetics/*metabolism MH - Epithelial Cells/enzymology/*metabolism/microbiology MH - Humans MH - Inflammasomes/genetics/*metabolism MH - Interleukin-18/genetics/metabolism MH - Interleukin-1beta/genetics/metabolism MH - Intestinal Mucosa/*metabolism/microbiology MH - Intracellular Signaling Peptides and Proteins/genetics/*metabolism MH - L-Lactate Dehydrogenase/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism MH - Occludin/genetics/metabolism MH - RNA-Seq MH - Tight Junction Proteins/genetics/*metabolism MH - Zonula Occludens-1 Protein/genetics/metabolism MH - beta-Defensins/metabolism MH - Cathelicidins OTO - NOTNLM OT - Antimicrobial peptides OT - Candida OT - Inflammasome OT - Intestinal barrier OT - Tight junction proteins EDAT- 2019/10/20 06:00 MHDA- 2021/07/27 06:00 CRDT- 2019/10/20 06:00 PHST- 2019/03/20 00:00 [received] PHST- 2019/09/26 00:00 [revised] PHST- 2019/10/07 00:00 [accepted] PHST- 2019/10/20 06:00 [pubmed] PHST- 2021/07/27 06:00 [medline] PHST- 2019/10/20 06:00 [entrez] AID - S1043-4666(19)30311-4 [pii] AID - 10.1016/j.cyto.2019.154882 [doi] PST - ppublish SO - Cytokine. 2020 Feb;126:154882. doi: 10.1016/j.cyto.2019.154882. Epub 2019 Oct 16.