TY - JOUR
T1 - Fibromyalgia and microglial TNF-α
T2 - Translational research using human blood induced microglia-like cells
AU - Ohgidani, Masahiro
AU - Kato, Takahiro A.
AU - Hosoi, Masako
AU - Tsuda, Makoto
AU - Hayakawa, Kohei
AU - Hayaki, Chie
AU - Iwaki, Rie
AU - Sagata, Noriaki
AU - Hashimoto, Ryota
AU - Inoue, Kazuhide
AU - Sudo, Nobuyuki
AU - Kanba, Shigenobu
N1 - Funding Information:
The authors would like to thank Ms Miwa Irie, Ms Aya Yamada, Mr. Shogo Inamine, Ms Yuka Matsushita and Dr. Mao Shibata for their technical assistance. This work was supported by Grant-in-Aid for Scientific Research on (1) Research Project on Elucidation of Chronic Pain from the Japan Agency for Medical Research and Development (AMED) (to M.H. & T.A.K.), (2) KAKENHI - the Japan Society for the Promotion of Science (26713039 to T.A.K. and 17K19915 to M.O.), (3) Innovative Areas “Glia Assembly” of The Ministry of Education, Culture, Sports, Science, and Technology, Japan (25117011 to S.K.), (4) Young Principal Investigators’ Research Grant of Innovation Center for Medical Redox Navigation, Kyushu University (to T.A.K.), and (5) SENSHIN Medical Research Foundation (to T.A.K., M.O., and S.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cells in the brain called microglia has attracted attention as a potential underlying pathological mechanism in chronic pain. Until recently, however, technological and ethical considerations have limited the ability to conduct research using human microglia. To overcome this limitation, we have recently developed a technique to create human-induced microglia-like (iMG) cells from human peripheral blood monocytes. In this study, we created the iMG cells from 14 patients with fibromyalgia and 10 healthy individuals, and compared the activation of iMG cells between two groups at the cellular level. The expression of tumor necrosis factor (TNF)-α at mRNA and protein levels significantly increased in ATP-stimulated iMG cells from patients with fibromyalgia compared to cells from healthy individuals. Interestingly, there was a moderate correlation between ATP-induced upregulation of TNF-α expression and clinical parameters of subjective pain and other mental manifestations of fibromyalgia. These findings suggest that microglia in patients with fibromyalgia are hypersensitive to ATP. TNF-α from microglia may be a key factor underlying the complex pathology of fibromyalgia.
AB - Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cells in the brain called microglia has attracted attention as a potential underlying pathological mechanism in chronic pain. Until recently, however, technological and ethical considerations have limited the ability to conduct research using human microglia. To overcome this limitation, we have recently developed a technique to create human-induced microglia-like (iMG) cells from human peripheral blood monocytes. In this study, we created the iMG cells from 14 patients with fibromyalgia and 10 healthy individuals, and compared the activation of iMG cells between two groups at the cellular level. The expression of tumor necrosis factor (TNF)-α at mRNA and protein levels significantly increased in ATP-stimulated iMG cells from patients with fibromyalgia compared to cells from healthy individuals. Interestingly, there was a moderate correlation between ATP-induced upregulation of TNF-α expression and clinical parameters of subjective pain and other mental manifestations of fibromyalgia. These findings suggest that microglia in patients with fibromyalgia are hypersensitive to ATP. TNF-α from microglia may be a key factor underlying the complex pathology of fibromyalgia.
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U2 - 10.1038/s41598-017-11506-4
DO - 10.1038/s41598-017-11506-4
M3 - Article
C2 - 28928366
AN - SCOPUS:85029838409
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 11882
ER -