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Kawasaki disease OX40–OX40L axis acts as an upstream regulator of NFAT signaling pathway

Background We investigated a costimulatory molecule OX40–OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). Methods One hundred and one samples were collected and divided into six groups: coronary artery lesion...

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Published in:Pediatric research 2019-05, Vol.85 (6), p.835-840
Main Authors: Lv, Yu-Wen, Chen, Ye, Lv, Hai-Tao, Li, Xuan, Tang, Yun-Jia, Qian, Wei-Guo, Xu, Qiu-Qin, Sun, Ling, Qian, Guang-Hui, Ding, Yue-Yue
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creator Lv, Yu-Wen
Chen, Ye
Lv, Hai-Tao
Li, Xuan
Tang, Yun-Jia
Qian, Wei-Guo
Xu, Qiu-Qin
Sun, Ling
Qian, Guang-Hui
Ding, Yue-Yue
description Background We investigated a costimulatory molecule OX40–OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). Methods One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. Results The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. Conclusion OX40–OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.
doi_str_mv 10.1038/s41390-019-0312-0
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Methods One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. Results The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. Conclusion OX40–OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/s41390-019-0312-0</identifier><identifier>PMID: 30723312</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Case-Control Studies ; Child, Preschool ; Clinical Research Article ; Female ; Humans ; Immunoglobulins, Intravenous - therapeutic use ; Infant ; Kawasaki disease ; Kinases ; Leukocytes, Mononuclear - immunology ; Male ; Medicine ; Medicine &amp; Public Health ; Mucocutaneous Lymph Node Syndrome - genetics ; Mucocutaneous Lymph Node Syndrome - immunology ; Mucocutaneous Lymph Node Syndrome - therapy ; NFATC Transcription Factors - blood ; NFATC Transcription Factors - genetics ; OX40 Ligand - blood ; OX40 Ligand - genetics ; Pediatric Surgery ; Pediatrics ; Protein expression ; Proteins ; Receptors, OX40 - blood ; Receptors, OX40 - genetics ; RNA, Messenger - blood ; RNA, Messenger - genetics ; Signal Transduction</subject><ispartof>Pediatric research, 2019-05, Vol.85 (6), p.835-840</ispartof><rights>International Pediatric Research Foundation, Inc 2019</rights><rights>2019© International Pediatric Research Foundation, Inc 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-dda151cdab0ebacf60ac0152858ea3a076a61a218a9e68a8cda44bc7081422773</citedby><cites>FETCH-LOGICAL-c415t-dda151cdab0ebacf60ac0152858ea3a076a61a218a9e68a8cda44bc7081422773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30723312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lv, Yu-Wen</creatorcontrib><creatorcontrib>Chen, Ye</creatorcontrib><creatorcontrib>Lv, Hai-Tao</creatorcontrib><creatorcontrib>Li, Xuan</creatorcontrib><creatorcontrib>Tang, Yun-Jia</creatorcontrib><creatorcontrib>Qian, Wei-Guo</creatorcontrib><creatorcontrib>Xu, Qiu-Qin</creatorcontrib><creatorcontrib>Sun, Ling</creatorcontrib><creatorcontrib>Qian, Guang-Hui</creatorcontrib><creatorcontrib>Ding, Yue-Yue</creatorcontrib><title>Kawasaki disease OX40–OX40L axis acts as an upstream regulator of NFAT signaling pathway</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background We investigated a costimulatory molecule OX40–OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). Methods One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. Results The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. 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Methods One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. Results The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. Conclusion OX40–OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30723312</pmid><doi>10.1038/s41390-019-0312-0</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Case-Control Studies
Child, Preschool
Clinical Research Article
Female
Humans
Immunoglobulins, Intravenous - therapeutic use
Infant
Kawasaki disease
Kinases
Leukocytes, Mononuclear - immunology
Male
Medicine
Medicine & Public Health
Mucocutaneous Lymph Node Syndrome - genetics
Mucocutaneous Lymph Node Syndrome - immunology
Mucocutaneous Lymph Node Syndrome - therapy
NFATC Transcription Factors - blood
NFATC Transcription Factors - genetics
OX40 Ligand - blood
OX40 Ligand - genetics
Pediatric Surgery
Pediatrics
Protein expression
Proteins
Receptors, OX40 - blood
Receptors, OX40 - genetics
RNA, Messenger - blood
RNA, Messenger - genetics
Signal Transduction
title Kawasaki disease OX40–OX40L axis acts as an upstream regulator of NFAT signaling pathway
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