PIM1 Signaling in Immunoinflammatory Diseases: an Emerging Therapeutic Target

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Oct 7

PMID 39372407

Authors

Xue Yang

Chunming Liu

Yuxi Lei

Zhi Liu

Bin Zhu

Dongchi Zhao

Affiliations

Soon will be listed here.

Abstract

PIM1, the proviral integration site for Moloney murine leukemia virus, is a member of the serine/threonine protein kinase family. It is involved in many biological events, such as cell survival, cell cycle progression, cell proliferation, and cell migration, and has been widely studied in malignant diseases. However, recent studies have shown that PIM1 plays a prominent role in immunoinflammatory diseases, including autoimmune uveitis, inflammatory bowel disease, asthma, and rheumatoid arthritis. PIM1 can function in inflammatory signal transduction by phosphorylating multiple inflammatory protein substrates and mediating macrophage activation and T lymphocyte cell specification, thus participating in the development of multiple immunoinflammatory diseases. Moreover, the inhibition of PIM1 has been demonstrated to ameliorate certain immunoinflammatory disorders. Based on these studies, we suggest PIM1 as a potential therapeutic target for immunoinflammatory diseases and a valid candidate for future research. Herein, for the first time, we provide a detailed review that focuses on the roles of PIM1 in the pathogenesis of immunoinflammatory diseases.

References

Schopf F, Biebl M, Buchner J . The HSP90 chaperone machinery. Nat Rev Mol Cell Biol. 2017; 18(6):345-360. DOI: 10.1038/nrm.2017.20. View

Cao H, Diao J, Liu H, Liu S, Liu J, Yuan J . The Pathogenicity and Synergistic Action of Th1 and Th17 Cells in Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2022; 29(5):818-829. DOI: 10.1093/ibd/izac199. View

Zhang Z, Xie S, Qian J, Gao F, Jin W, Wang L . Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl efflux signaling pathway. J Transl Med. 2023; 21(1):452. PMC: 10329339. DOI: 10.1186/s12967-023-04313-1. View

Wu K, Yuan Y, Yu H, Dai X, Wang S, Sun Z . The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice. Blood. 2020; 136(4):501-515. PMC: 7378459. DOI: 10.1182/blood.2019003990. View

Peltola K, Paukku K, Aho T, Ruuska M, Silvennoinen O, Koskinen P . Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3. Blood. 2004; 103(10):3744-50. DOI: 10.1182/blood-2003-09-3126. View

Mizuno K, Shirogane T, Shinohara A, Iwamatsu A, Hibi M, Hirano T . Regulation of Pim-1 by Hsp90. Biochem Biophys Res Commun. 2001; 281(3):663-9. DOI: 10.1006/bbrc.2001.4405. View

Shay K, Wang Z, Xing P, McKenzie I, Magnuson N . Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway. Mol Cancer Res. 2005; 3(3):170-81. DOI: 10.1158/1541-7786.MCR-04-0192. View

Panchal N, Sabina E . A serine/threonine protein PIM kinase as a biomarker of cancer and a target for anti-tumor therapy. Life Sci. 2020; 255:117866. DOI: 10.1016/j.lfs.2020.117866. View

Shin Y, Takeda K, Shiraishi Y, Jia Y, Wang M, Jackson L . Inhibition of Pim1 kinase activation attenuates allergen-induced airway hyperresponsiveness and inflammation. Am J Respir Cell Mol Biol. 2011; 46(4):488-97. PMC: 3359953. DOI: 10.1165/rcmb.2011-0190OC. View

10.

Gu C, Liu Y, Lv J, Zhang C, Huang Z, Jiang Q . Kurarinone regulates Th17/Treg balance and ameliorates autoimmune uveitis via Rac1 inhibition. J Adv Res. 2024; 69:381-398. DOI: 10.1016/j.jare.2024.03.013. View

11.

Pan X, Wang H, Tong D, Li Y, Huang L, Wang C . miRNA-370 acts as a tumor suppressor via the downregulation of PIM1 in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 2017; 21(6):1254-1263. View

12.

Aho T, Sandholm J, Peltola K, Ito Y, Koskinen P . Pim-1 kinase phosphorylates RUNX family transcription factors and enhances their activity. BMC Cell Biol. 2006; 7:21. PMC: 1473194. DOI: 10.1186/1471-2121-7-21. View

13.

Pazdrak K, Moon Y, Straub C, Stafford S, Kurosky A . Eosinophil resistance to glucocorticoid-induced apoptosis is mediated by the transcription factor NFIL3. Apoptosis. 2016; 21(4):421-31. PMC: 4769953. DOI: 10.1007/s10495-016-1226-5. View

14.

Locati M, Curtale G, Mantovani A . Diversity, Mechanisms, and Significance of Macrophage Plasticity. Annu Rev Pathol. 2019; 15:123-147. PMC: 7176483. DOI: 10.1146/annurev-pathmechdis-012418-012718. View

15.

Boulet L, Gupta S, FitzGerald J . Inhaled Glucocorticoids in Asthma. N Engl J Med. 2018; 378(21):2050-1. DOI: 10.1056/NEJMc1804801. View

16.

Wildner G, Diedrichs-Mohring M . Resolution of uveitis. Semin Immunopathol. 2019; 41(6):727-736. DOI: 10.1007/s00281-019-00758-z. View

17.

Wang J, Cao Y, Liu Y, Zhang X, Ji F, Li J . PIM1 inhibitor SMI-4a attenuated lipopolysaccharide-induced acute lung injury through suppressing macrophage inflammatory responses via modulating p65 phosphorylation. Int Immunopharmacol. 2019; 73:568-574. DOI: 10.1016/j.intimp.2019.05.040. View

18.

Van Raemdonck K, Umar S, Palasiewicz K, Volkov S, Volin M, Arami S . CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteoclast formation in rheumatoid arthritis. Cell Mol Life Sci. 2019; 77(7):1387-1399. PMC: 10040247. DOI: 10.1007/s00018-019-03235-w. View

19.

Huang Y, Tian C, Li Q, Xu Q . Knockdown Inhibits LPS/IFN-γ-Induced M1 Macrophage Polarization through the NF-κB Pathway in THP-1 Cells. Int J Mol Sci. 2019; 20(8). PMC: 6514734. DOI: 10.3390/ijms20082023. View

20.

Wang R, Zhu L, Li H, Peng X, Zhao S, Su W . Single-Cell transcriptomes of immune cells provide insights into the therapeutic effects of mycophenolate mofetil on autoimmune uveitis. Int Immunopharmacol. 2023; 119:110223. DOI: 10.1016/j.intimp.2023.110223. View