PMID- 34929700
OWN - NLM
STAT- MEDLINE
DCOM- 20220519
LR  - 20220626
IS  - 1423-0135 (Electronic)
IS  - 1018-1172 (Linking)
VI  - 59
IP  - 3
DP  - 2022
TI  - Recombinant Human Soluble Thrombomodulin Suppresses Arteritis in a Mouse Model of 
      Kawasaki Disease.
PG  - 176-188
LID - 10.1159/000520717 [doi]
AB  - INTRODUCTION AND OBJECTIVE: Kawasaki disease (KD) is associated with diffuse and 
      systemic vasculitis of unknown aetiology and primarily affects infants and 
      children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of 
      developing coronary aneurysms, but some children have IVIG-resistant KD, which 
      increases their risk of developing coronary artery injury. Here, we investigated 
      the effect of recombinant human soluble thrombomodulin (rTM), which has 
      anticoagulant, anti-inflammatory, and cytoprotective properties on the 
      development of coronary arteritis in a mouse model of vasculitis. METHODS: An 
      animal model of KD-like vasculitis was created by injecting mice with Candida 
      albicans water-soluble fraction (CAWS). This model was used to investigate the 
      mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-alpha), and 
      tissue factor (TF), in addition to histopathology of heart tissues. RESULTS: rTM 
      treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 
      days after CAWS treatment. In addition, mRNA expression analysis revealed that 
      rTM administration increased cardiac IL-10 expression until day 27, whereas 
      expression of TNF-alpha was unaffected. Moreover, in the spleen, rTM treatment 
      restores IL-10 and TF expression to normal levels. CONCLUSION: These findings 
      suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. 
      Therefore, rTM may be an effective treatment for KD.
CI  - (c) 2021 S. Karger AG, Basel.
FAU - Nakayama, Hironobu
AU  - Nakayama H
AD  - Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, 
      Japan.
FAU - Inada, Hiroyasu
AU  - Inada H
AD  - Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, 
      Japan.
FAU - Inukai, Tatsuya
AU  - Inukai T
AD  - Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, 
      Japan.
AD  - Department of Microbiology, Tokyo Medical University, Shinjuku-ku, Japan.
FAU - Kondo, Kenta
AU  - Kondo K
AD  - Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, 
      Japan.
AD  - Medicine Department, Suzuka Kaisei Hospital, Suzuka, Japan.
FAU - Hirai, Kazuyuki
AU  - Hirai K
AD  - Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, 
      Japan.
FAU - Tsutsumi, Tomonari
AU  - Tsutsumi T
AD  - Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, 
      Japan.
FAU - Adachi, Yoshiyuki
AU  - Adachi Y
AD  - School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, 
      Japan.
FAU - Nagi-Miura, Noriko
AU  - Nagi-Miura N
AD  - School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, 
      Japan.
FAU - Ohno, Naohito
AU  - Ohno N
AD  - School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, 
      Japan.
FAU - Suzuki, Koji
AU  - Suzuki K
AD  - Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20211220
PL  - Switzerland
TA  - J Vasc Res
JT  - Journal of vascular research
JID - 9206092
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thrombomodulin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - *Arteritis/drug therapy/pathology
MH  - Candida albicans/metabolism
MH  - Coronary Vessels/metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Immunoglobulins, Intravenous
MH  - Interleukin-10
MH  - Mice
MH  - *Mucocutaneous Lymph Node Syndrome/drug therapy
MH  - RNA, Messenger
MH  - Recombinant Proteins/therapeutic use
MH  - *Thrombomodulin/therapeutic use
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - *Vasculitis/drug therapy/prevention & control
OTO - NOTNLM
OT  - Anti-inflammatory functions
OT  - Candida albicans water-soluble fraction
OT  - Kawasaki disease
OT  - Recombinant human soluble thrombomodulin
OT  - Vasculitis
EDAT- 2021/12/21 06:00
MHDA- 2022/05/20 06:00
CRDT- 2021/12/20 20:32
PHST- 2021/06/30 00:00 [received]
PHST- 2021/10/28 00:00 [accepted]
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2022/05/20 06:00 [medline]
PHST- 2021/12/20 20:32 [entrez]
AID - 000520717 [pii]
AID - 10.1159/000520717 [doi]
PST - ppublish
SO  - J Vasc Res. 2022;59(3):176-188. doi: 10.1159/000520717. Epub 2021 Dec 20.