ALPK1 affects testosterone mediated regulation of proinflammatory cytokines production.
Alpha-protein kinase 1, also known as alpha-kinase 1 (ALPK1), is associated with chronic kidney disease (CKD), myocardial infarction, gout and type 2 diabetes mellitus (DM). In addition to having an inductive effect on the proinflammatory cytokines in monocytic THP1 cells, ALPK1 is expressed abundantly in the mouse testes. Low testosterone levels are commonly associated with arthritis, CKD, type 2 DM, cardiovascular disease and inflammation. The testosterone's anti-inflammatory effect has been demonstrated to reduce proinflammatory cytokines and adhesion molecules. In this study, we found that ALPK1 transgenic mice showed lower levels of testosterone in both the testes and the serum. Decreasing endogenous ALPK1 enhanced testosterone levels and transcripts of testosterone-regulated genes (P450scc, 3beta-HSD, P450C17, 17beta-HSD, StAR, and INSL3) in TM3 Leydig cells. In contrast, increasing testosterone decreased ALPK1 in both TM3 and monocytic THP1 cells. This decrease was accompanied by a reduction of the proinflammatory cytokines. Increased ALPK1 levels attenuated the testosterone effects in THP1 cells. Finally, we also found that ALPK1 increased the release of TNF-alpha and TGF-beta1 in the human embryonic kidney 293 cells, while testosterone inhibited ALPK1 in the primary kidney cells. Taken together, this data suggests that the balance between ALPK1 and testosterone plays a critical role in the testosterone-mediated inhibition of proinflammatory cytokines.
Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Tzer-Min
TM
Kuo
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
Kun-Tu
KT
Yeh
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
Hui-Ting
HT
Hsu
Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan; Department of Health Risk Management, College of Management, China Medical University, Taiwan.
Shang-Lun
SL
Chiang
Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan.
Jan-Gowth
JG
Chang
Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
Chung-Ming
CM
Huang
Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hung-Pin
HP
Tu
Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan.
Chiu-Shong
CS
Liu
Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. Electronic address: ycko0406@gmail.com.
Ying-Chin
YC
Ko
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011494:Protein Kinases / Q000378:metabolism*; D013739:Testosterone / Q000502:physiology*
D016207:Cytokines; D018836:Inflammation Mediators; D013739:Testosterone; C000604235:ALPK1 protein, mouse; D011494:Protein Kinases
ALPK1; Chronic inflammation; Proinflammatory cytokines; Testosterone