PMID- 33820486
OWN - NLM
STAT- MEDLINE
DCOM- 20211110
LR  - 20220421
IS  - 1525-6049 (Electronic)
IS  - 0886-022X (Print)
IS  - 0886-022X (Linking)
VI  - 43
IP  - 1
DP  - 2021 Dec
TI  - Inhibitory effect of anti-malarial agents on the expression of proinflammatory 
      chemokines via Toll-like receptor 3 signaling in human glomerular endothelial 
      cells.
PG  - 643-650
LID - 10.1080/0886022X.2021.1908901 [doi]
AB  - OBJECTIVE: Although anti-malarial agents, chloroquine (CQ) and hydroxychloroquine 
      (HCQ) are currently used for the treatment of systemic lupus erythematosus, their 
      efficacy for lupus nephritis (LN) remains unclear. Given that upregulation of 
      glomerular Toll-like receptor 3 (TLR3) signaling plays a pivotal role in the 
      pathogenesis of LN, we examined whether CQ and HCQ affect the expression of the 
      TLR3 signaling-induced representative proinflammatory chemokines, monocyte 
      chemoattractant protein-1 (MCP-1), and C-C motif chemokine ligand 5 (CCL5) in 
      cultured human glomerular endothelial cells (GECs). METHODS: We examined the 
      effect of polyinosinic-polycytidylic acid (poly IC), an agonist of TLR3, on 
      MCP-1, CCL5 and interferon (IFN)-beta expression in GECs. We then analyzed whether 
      pretreatment with CQ, HCQ, or dexamethasone (DEX) inhibits poly IC-induced 
      expression of these chemokines using real-time quantitative reverse transcriptase 
      PCR and ELISA. Phosphorylation of signal transducers and activator of 
      transcription protein 1 (STAT1) was examined using western blotting. RESULTS: 
      Poly IC increased MCP-1 and CCL5 expression in a time- and 
      concentration-dependent manner in GECs. Pretreating cells with CQ, but not DEX, 
      attenuated poly IC-induced MCP-1 and CCL5 expression; however, HCQ pretreatment 
      attenuated poly IC-induced CCL5, but not MCP-1. HCQ did not affect the expression 
      of IFN-beta and phosphorylation of STAT-1. CONCLUSION: Considering that TLR3 
      signaling is implicated, at least in part, in LN pathogenesis, our results 
      suggest that anti-malarial agents exert a protective effect against the 
      development of inflammation in GECs, as postulated in LN. Interestingly, CQ is a 
      rather powerful inhibitor compared with HCQ on TLR3 signaling-induced chemokine 
      expression in GECs. In turn, these findings may further support the theory that 
      the use of HCQ is safer than CQ in a clinical setting. However, further detailed 
      studies are needed to confirm our preliminary findings.
FAU - Sato, Riko
AU  - Sato R
AD  - Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
FAU - Imaizumi, Tadaatsu
AU  - Imaizumi T
AD  - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, Japan.
FAU - Aizawa, Tomomi
AU  - Aizawa T
AD  - Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
FAU - Watanabe, Shojiro
AU  - Watanabe S
AD  - Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
FAU - Tsugawa, Koji
AU  - Tsugawa K
AD  - Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
FAU - Kawaguchi, Shogo
AU  - Kawaguchi S
AD  - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, Japan.
FAU - Seya, Kazuhiko
AU  - Seya K
AD  - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, Japan.
FAU - Matsumiya, Tomoh
AU  - Matsumiya T
AD  - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 
      Hirosaki, Japan.
FAU - Tanaka, Hiroshi
AU  - Tanaka H
AD  - Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
AD  - Faculty of Education, Department of School Health Science, Hirosaki University, 
      Hirosaki, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Ren Fail
JT  - Renal failure
JID - 8701128
RN  - 0 (Antimalarials)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines)
RN  - 0 (TLR3 protein, human)
RN  - 0 (Toll-Like Receptor 3)
RN  - 77238-31-4 (Interferon-beta)
RN  - 886U3H6UFF (Chloroquine)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Antimalarials/*pharmacology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemokine CCL5/genetics/*metabolism
MH  - Chemokines/*genetics
MH  - Chloroquine/pharmacology
MH  - Endothelial Cells/*metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Interferon-beta/metabolism
MH  - Kidney Glomerulus/cytology
MH  - Lupus Nephritis/drug therapy
MH  - Poly I-C/metabolism/pharmacology
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 3/genetics/*metabolism
PMC - PMC8032345
OTO - NOTNLM
OT  - Chloroquine
OT  - Toll-like receptor 3
OT  - glomerular endothelial cells
OT  - hydroxychloroquine
OT  - lupus nephritis
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2021/04/07 06:00
MHDA- 2021/11/11 06:00
PMCR- 2021/04/05
CRDT- 2021/04/06 05:20
PHST- 2021/04/06 05:20 [entrez]
PHST- 2021/04/07 06:00 [pubmed]
PHST- 2021/11/11 06:00 [medline]
PHST- 2021/04/05 00:00 [pmc-release]
AID - 1908901 [pii]
AID - 10.1080/0886022X.2021.1908901 [doi]
PST - ppublish
SO  - Ren Fail. 2021 Dec;43(1):643-650. doi: 10.1080/0886022X.2021.1908901.