PSTPIP2 is associated with disease severity in patients with pressure ulcer sepsis and has anti-inflammatory effects

Main Article Content

Xiaoxia Wang
Youli Wang
Jianjun Luo
Lipeng Wang
Liye Guo
Xinxin Zhu

Keywords

correlation, Inflammation, NF-κB, patients with -pressure ulcer sepsis, PSTPIP2

Abstract

Background: One of the common adverse reactions in patients with pressure ulcers (PU) is sepsis, which is mainly related to microbial infections caused by pathogenic organisms. The activation of nuclear factor kappa-B (NF-κB) frequently occurs in conjunction with pathogenic microbial infections. Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is closely related to inflammatory disorders. The role and mechanism of PSTPIP2 in sepsis because of pressure ulcers is unclear. In this study, we discovered that PSTPIP2 was lowly expressed in peripheral blood of patients with sepsis induced by pressure ulcers.


Methods: Peripheral blood was collected from 20 patients with sepsis due to pressure ulcers and 10 healthy controls, and the expression of PSTPIP2 in peripheral blood was discovered by polymerase chain reaction and Western blot analysis. Information on the clinical characteristics of patients was summarized, and the expression data of PSTPIP2 were correlated with the patients’ acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and C-reactive protein (CRP) and procalcitonin (PCT) scores by Spearman’s correlation analysis. One of the main mediators of Gram-negative sepsis is lipopolysaccharide (LPS). In order to establish an in vitro sepsis model, THP-1 cells were treated with LPS, and the cells were transfected with PSTPIP2. Contents of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α) in each group of cells were detected by enzyme-linked--immunosorbent serologic assay, and NF-κB-related proteins were detected by Western blot analysis.


Results: When compared to healthy controls, the peripheral blood of patients with pressure sepsis had lower PSTPIP2 expression, which had a negative correlation with the APACHE II, SOFA, CRP, and PCT scores. LPS-induced THP-1 cells expressed less PSTPIP2 than the untreated control cells, and PSTPIP2 transfection decreased IL-6, IL-1β, and TNF-α levels and inhibited the activation of NF-κB pathway.


Conclusion: PSTPIP2 is associated with disease severity in patients with pressure ulcer sepsis and has anti-inflammatory effects.

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References

1. Okamoto S, Ogai K, Mukai K, Sugama J. Association of skin microbiome with the onset and recurrence of pressure injury in bedridden elderly people. Microorganisms. 2021;9(8):1603. 10.3390/microorganisms9081603

2. Kumar S, Theis T, Tschang M, Nagaraj V, Berthiaume F. Reactive oxygen species and pressure ulcer formation after traumatic injury to spinal cord and brain. Antioxidants (Basel, Switzerland). 2021;10(7): 1013. 10.3390/antiox10071013

3. Espejo E, Andrés M, Borrallo RM, Padilla E, Garcia-Restoy E, Bella F. Bacteremia associated with pressure ulcers: A prospective cohort study. Eur J Clin Microbiol Infect Dis. 2018;37(5):969–75. 10.1007/s10096-018-3216-8

4. Schiffman J, Golinko MS, Yan A, Flattau A, Tomic-Canic M, Brem H. Operative debridement of pressure ulcers. World J Surg. 2009;33(7):1396–402. 10.1007/s00268-009-0024-4

5. Kim Y, Lee J, Lee S, Kim W. Use of quick sequential organ failure assessment score-based sepsis clinical decision support system may be helpful to predict sepsis development. Signa Vitae. 2021;17(5):86–94. 10.22514/sv.2021.082

6. D’Elia RV, Harrison K, Oyston PC, Lukaszewski RA, Clark GC. Targeting the “cytokine storm” for therapeutic benefit. Clin Vaccine Immunol (CVI). 2013;20(3):319–27. 10.1128/CVI.00636-12

7. Raymond SL, Holden DC, Mira JC, Stortz JA, Loftus TJ, Mohr AM, et al. Microbial recognition and danger signals in sepsis and trauma. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10, Pt B):2564–73. 10.1016/j.bbadis.2017.01.013

8. Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019;20(21): e420-e427. 10.3390/ijms20215376

9. Zhu H, Jiang W, Zhao H, He C, Tang X, Xu S, et al. PSTPIP2 inhibits cisplatin-induced acute kidney injury by suppressing apoptosis of renal tubular epithelial cells. Cell Death Dis. 2020;11(12):1057. 10.1038/s41419-020-03267-2

10. Li M, Xiao YB, Wang XT, Zhuang JP, Zhou CL. Proline-serine-threonine phosphatase-interacting protein 2 alleviates diabetes mellitus-osteoarthritis in rats through attenuating synovial inflammation and cartilage injury. Orthop Surg. 2021;13(4):1398–407. 10.1111/os.13000

11. Yang Y, Wu XQ, Li WX, Huang HM, Li HD, Pan XY, et al. PSTPIP2 connects DNA methylation to macrophage polarization in CCL4-induced mouse model of hepatic fibrosis. Oncogene. 2018;37(47):6119–35. 10.1038/s41388-018-0383-0

12. Yao Y, Yu H, Liu Y, Xu Q, Li X, Meng X, et al. PSTPIP2 inhibits the inflammatory response and proliferation of fibroblast--like synoviocytes in vitro. Front Pharmacol. 2018;9:1432. 10.3389/fphar.2018.01432

13. Cao L, Zhu T, Lang X, Jia S, Yang Y, Zhu C, et al. Inhibiting DNA methylation improves survival in severe sepsis by regulating nf-κb pathway. Front Immunol. 2020;11:1360. 10.3389/fimmu.2020.01360

14. Böhrer H, Qiu F, Zimmermann T, Zhang Y, Jllmer T, Männel D, et al. Role of NF-kappaB in the mortality of sepsis. J Clin Invest. 1997;100(5):972–85. 10.1172/JCI119648

15. Ikezoe T, Yang Y, Heber D, Taguchi H, Koeffler HP. PC-SPES: A potent inhibitor of nuclear factor-kappa B rescues mice from lipopolysaccharide-induced septic shock. Mol Pharmacol. 2003;64(6):1521–9. 10.1124/mol.64.6.1521

16. Ling P, Tang R, Wang H, Deng X, Chen J. miR-1184 Regulates inflammatory responses and cell apoptosis by targeting TRADD in an LPS-induced cell model of sepsis. Exp Ther Med. 2021;21(6):630. 10.3892/etm.2021.10062

17. Lai K, Song C, Gao M, Deng Y, Lu Z, Li N, et al. Uridine-alleviates sepsis-induced acute lung injury by inhibiting ferroptosis of macrophage. Int J Mol Sci. 2023;24(6):5093. 10.3390/ijms24065093

18. Liao HJ, Chyuan IT, Wu CS, Lin SW, Chen KH, Tsai HF, et al. Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice. Rheumatology (Oxford, England). 2015;54(7):1317–26. 10.1093/rheumatology/keu481

19. Liu L, Zhang S, Wang Y, Bao W, Zhou Y, Dang W, et al. BIG1 controls macrophage pro-inflammatory responses through ARF3-mediated PI(4,5)P2 synthesis. Cell Death Dis. 2020;11(5):374. 10.1038/s41419-020-2590-1

20. Philip S, Tom G, Balakrishnan Nair P, Sundaram S, Velikkakathu Vasumathy A. Tinospora cordifolia chloroform extract inhibits LPS-induced inflammation via NF-κB inactivation in THP-1 cells and improves survival in sepsis. BMC Complement Med Ther. 2021;21(1):97. 10.1186/s12906-021-03244-y

21. Bisht A, Dickens M, Rutherfurd-Markwick K, Thota R, Mutukumira AN, Singh H. Chlorogenic acid potentiates the anti-inflammatory activity of curcumin in LPS-stimulated THP-1 cells. Nutrients. 2020;12(9): 2706. 10.3390/nu12092706

22. Li Y, Lin B. Icariside II regulates TLR4/NF-κB signaling pathway to improve septic lung injury. Signa Vitae. 2021;17(6): 136–42. 10.22514/sv.2021.216