PMID- 37688871
OWN - NLM
STAT- MEDLINE
DCOM- 20230920
LR  - 20230920
IS  - 1873-3336 (Electronic)
IS  - 0304-3894 (Linking)
VI  - 460
DP  - 2023 Oct 15
TI  - Fibroblast-derived CXCL14 aggravates crystalline silica-induced pulmonary 
      fibrosis by mediating polarization and recruitment of interstitial macrophages.
PG  - 132489
LID - S0304-3894(23)01772-7 [pii]
LID - 10.1016/j.jhazmat.2023.132489 [doi]
AB  - Exposure to crystalline silica (CS) particles in worksites and dwellings can lead 
      to silicosis due to excessive fibroblast activation. Considering their 
      immuno-regulatory activities, the contribution of pulmonary fibroblasts in the 
      progression of silicosis has not been thoroughly characterized. Here, we 
      demonstrate that exposure of the lung to CS particles leads to the upregulation 
      of fibroblast-derived C-X-C motif chemokine ligand 14 (CXCL14). By employing an 
      in vitro co-culture system, we demonstrated activated fibroblasts recruited bone 
      marrow-derived macrophages (BMDMs) and favored alternative macrophage 
      polarization (M2) mediated by CXCL14. Furthermore, in vivo studies echoed that 
      systemic CXCL14 neutralizing or fibroblast-specific Cxcl14 knockout proved CXCL14 
      was indispensable for the recruitment and phenotype alteration of lung 
      macrophages, especially interstitial macrophages (IMs), under stimulation by CS 
      particles. Mechanistically, we showed that GLI2 and p21-mediated cellular 
      senescence were mediators of CXCL14 production following CS exposure. 
      Accordingly, GLI2 blockage and countering cellular senescence by reviving 
      PINK1-mediated mitophagy may be efficient strategies to reduce CXCL14 expression 
      in activated fibroblasts during silicosis. Our findings emphasize the 
      immuno-regulatory function of fibroblasts in silicosis via CXCL14, providing 
      intervention targets for CS-induced pulmonary fibrosis.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - You, Yichuan
AU  - You Y
AD  - Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention 
      (China Medical University), Ministry of Education, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang 110122, PR China; Department of Occupational and 
      Environmental Health, School of Public Health, China Medical University, No. 77 
      Puhe Road, Shenyang North New Area, Shenyang 110122, PR China.
FAU - Yuan, Haoyang
AU  - Yuan H
AD  - Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention 
      (China Medical University), Ministry of Education, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang 110122, PR China; Department of Occupational and 
      Environmental Health, School of Public Health, China Medical University, No. 77 
      Puhe Road, Shenyang North New Area, Shenyang 110122, PR China.
FAU - Min, Hui
AU  - Min H
AD  - Department of Immunology, College of Basic Medical Sciences, China Medical 
      University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, PR China.
FAU - Li, Chao
AU  - Li C
AD  - Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention 
      (China Medical University), Ministry of Education, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang 110122, PR China; Department of Occupational and 
      Environmental Health, School of Public Health, China Medical University, No. 77 
      Puhe Road, Shenyang North New Area, Shenyang 110122, PR China. Electronic 
      address: lichao@cmu.edu.cn.
FAU - Chen, Jie
AU  - Chen J
AD  - Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention 
      (China Medical University), Ministry of Education, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang 110122, PR China; Department of Occupational and 
      Environmental Health, School of Public Health, China Medical University, No. 77 
      Puhe Road, Shenyang North New Area, Shenyang 110122, PR China. Electronic 
      address: jchen@cmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230908
PL  - Netherlands
TA  - J Hazard Mater
JT  - Journal of hazardous materials
JID - 9422688
RN  - 7631-86-9 (Silicon Dioxide)
RN  - 0 (CXCL14 protein, human)
RN  - 0 (Chemokines, CXC)
SB  - IM
MH  - Humans
MH  - *Pulmonary Fibrosis/chemically induced
MH  - Silicon Dioxide/toxicity
MH  - Macrophages
MH  - *Silicosis
MH  - Fibroblasts
MH  - Chemokines, CXC
OTO - NOTNLM
OT  - CXCL14
OT  - Crystalline silica
OT  - Fibroblasts
OT  - Macrophages
OT  - Pulmonary fibrosis
COIS- Declaration of Competing Interest Authors declare that (1) Animal use has been 
      approved by the Animal Use and Care Committee at China Medical University with a 
      protocol number of CMU2021405. (2) All experiments and surgical procedures were 
      carried out in accordance with the National Institute of Health Guide for the 
      Care and Use of Laboratory Animals (NIH Publications No. 80-23) revised 1996. (3) 
      All efforts have been made to minimize the number of animals used and their 
      suffering. (4) There is no conflict of interest. (5) The work described was 
      original research that has not been published previously.
EDAT- 2023/09/10 00:41
MHDA- 2023/09/20 06:42
CRDT- 2023/09/09 18:02
PHST- 2023/06/29 00:00 [received]
PHST- 2023/08/29 00:00 [revised]
PHST- 2023/09/03 00:00 [accepted]
PHST- 2023/09/20 06:42 [medline]
PHST- 2023/09/10 00:41 [pubmed]
PHST- 2023/09/09 18:02 [entrez]
AID - S0304-3894(23)01772-7 [pii]
AID - 10.1016/j.jhazmat.2023.132489 [doi]
PST - ppublish
SO  - J Hazard Mater. 2023 Oct 15;460:132489. doi: 10.1016/j.jhazmat.2023.132489. Epub 
      2023 Sep 8.