PMID- 28658176 OWN - NLM STAT- MEDLINE DCOM- 20170717 LR - 20210109 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 96 IP - 26 DP - 2017 Jun TI - Circulating fibrocytes are involved in inflammation and leukocyte trafficking in neonates with necrotizing enterocolitis. PG - e7400 LID - 10.1097/MD.0000000000007400 [doi] LID - e7400 AB - Fibrocytes, ahematopoietic stem cell source of fibroblasts/myofibroblasts, were previously implicated to infiltrate into the intestinal and enhance inflammation.The aims of the present study were to elucidate the role of fibrocytes in necrotizing enterocolitis (NEC) pathogenesis and to explore the mechanisms by which fibrocytes contributed to the inflammatory responses.We investigated circulating and intestinal local fibrocytes from 32 patients with NEC, 8 patients with noninflammatory conditions of the gastrointestinal tract and 12 normal subjects.Significantly higher numbers of circulating fibrocytes were found in the peripheral blood from NEC patients than the controls (P < .01). Numerous fibrocytes were found infiltrating the NEC intestinal mucous membranes. The percentage of fibrocytes to total leukocytes in the NEC inflammatory lesions was significantly increased compared with the percentage in the noninflammatory gastrointestinal tract. The fibrocyte attractant chemokine C-X-C motif chemokine ligand 12 (CXCL12) was significantly increased in the plasma and was detectable in 80% of the peritoneal lavage fluid from NEC patients but not the controls. Furthermore, chemokine expression was increased in fibrocytes infiltrating and trafficking to leukocyte sites. In culture, lipopolysaccharide (LPS) induced a significant increase in the expression of the Toll-like receptor (TLR4) signal, with the upregulation of p38 in both the isolated fibrocytes and macrophages. Similarly, interleukin (IL)-1beta induced increased the upregulation of the IL-6, tumor necrosis factor (TNF)-alpha, and intercellular cell adhesion molecule-1 mRNAs but downregulated ColI in fibrocytes isolated from NEC patients compared with the controls.These findings indicate that circulating fibrocytes are increased in NEC patients and may be recruited to the inflammatory intestinal track, most likely through the CXCR4/CXCL12 axis. These cells may contribute to intestinal inflammation through TLR4 signaling by producing the TNF-alpha and IL-6 cytokines. FAU - Liu, Ye AU - Liu Y AD - Department of Neonatal, Children's Hospital, Chongqing Medical University, Chongqing Department of Pathology, Linyi People's Hospital, Linyi, Shandong Province Department of Pediatric General Surgery Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University Department of Neonatology, Yongchuan Hospital, Chongqing Medical University, Chongqing, P.R. China. FAU - Qingjuan, Shang AU - Qingjuan S FAU - Gao, Zongwei AU - Gao Z FAU - Deng, Chun AU - Deng C FAU - Wang, Yan AU - Wang Y FAU - Guo, Chunbao AU - Guo C LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Biomarkers) RN - 0 (CXCL12 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (ICAM1 protein, human) RN - 0 (IL1B protein, human) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Biomarkers/blood MH - Cell Count MH - Cell Movement/physiology MH - Cells, Cultured MH - Chemokine CXCL12/blood MH - Enterocolitis, Necrotizing/*blood/*immunology/pathology/surgery MH - Humans MH - Infant, Newborn MH - Intercellular Adhesion Molecule-1/blood MH - Interleukin-1beta/blood MH - Interleukin-6/blood MH - Leukocytes/*immunology/pathology MH - Lipopolysaccharides MH - RNA, Messenger/blood MH - Toll-Like Receptor 4/blood MH - Tumor Necrosis Factor-alpha/blood MH - p38 Mitogen-Activated Protein Kinases/blood PMC - PMC5500098 EDAT- 2017/06/29 06:00 MHDA- 2017/07/18 06:00 PMCR- 2017/06/30 CRDT- 2017/06/29 06:00 PHST- 2017/06/29 06:00 [entrez] PHST- 2017/06/29 06:00 [pubmed] PHST- 2017/07/18 06:00 [medline] PHST- 2017/06/30 00:00 [pmc-release] AID - 00005792-201706300-00084 [pii] AID - MD-D-17-01945 [pii] AID - 10.1097/MD.0000000000007400 [doi] PST - ppublish SO - Medicine (Baltimore). 2017 Jun;96(26):e7400. doi: 10.1097/MD.0000000000007400.