Upregulation of Lipocalin-2 in the Retina of Experimental Autoimmune Uveitis

Overview

Journal J Vet Med Sci

Date 2025 Feb 5

PMID 39909419

Authors

Hyeonju Kim

Meejung Ahn

Kyungsook Jung

Sungmoo Hong

Deokho Ko

Taeyoung Kang

Taekyun Shin

Jeongtae Kim

Affiliations

Soon will be listed here.

Abstract

Lipocalin-2, a siderophore-binding protein, is an antimicrobial, exerting both pro-inflammatory and anti-inflammatory actions. Lipocalin-2 is also involved in glial activation, matrix metalloproteinase stabilization, and cellular iron flux, all of which play roles in autoimmune diseases. The present study aimed to determine the expression of lipocalin-2 in the eyes of Lewis rats with interphotoreceptor-binding protein-induced experimental autoimmune uveitis (EAU). Significantly elevated serum lipocalin-2 levels were also detected in rats by enzyme-linked immunosorbent assay (ELISA). Lipocalin-2 immunostaining was detected predominantly in activated glial cells, including glutamine synthase-positive Müller cells, and ionized calcium-binding adaptor molecule 1-positive microglia and macrophages in EAU rats. Taken together, the results presented herein show that lipocalin-2 is a potential diagnostic marker for uveitis.

References

Jaberi S, Cohen A, DSouza C, Abdulrazzaq Y, Ojha S, Bastaki S . Lipocalin-2: Structure, function, distribution and role in metabolic disorders. Biomed Pharmacother. 2021; 142:112002. DOI: 10.1016/j.biopha.2021.112002. View

Kim J, Ahn M, Choi Y, Shin T . Upregulation of Cathepsins in Olfactory Bulbs Is Associated with Transient Olfactory Dysfunction in Mice with Experimental Autoimmune Encephalomyelitis. Mol Neurobiol. 2020; 57(8):3412-3423. DOI: 10.1007/s12035-020-01952-z. View

Dekens D, Eisel U, Gouweleeuw L, Schoemaker R, De Deyn P, Naude P . Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases. Ageing Res Rev. 2021; 70:101414. DOI: 10.1016/j.arr.2021.101414. View

Borkham-Kamphorst E, Van de Leur E, Zimmermann H, Karlmark K, Tihaa L, Haas U . Protective effects of lipocalin-2 (LCN2) in acute liver injury suggest a novel function in liver homeostasis. Biochim Biophys Acta. 2013; 1832(5):660-73. DOI: 10.1016/j.bbadis.2013.01.014. View

Shashidharamurthy R, Machiah D, Aitken J, Putty K, Srinivasan G, Chassaing B . Differential role of lipocalin 2 during immune complex-mediated acute and chronic inflammation in mice. Arthritis Rheum. 2013; 65(4):1064-73. PMC: 3618508. DOI: 10.1002/art.37840. View

Wildner G, Diedrichs-Mohring M, Thurau S . Rat models of autoimmune uveitis. Ophthalmic Res. 2008; 40(3-4):141-4. DOI: 10.1159/000119865. View

Nam Y, Kim J, Seo M, Kim J, Jin M, Jeon S . Lipocalin-2 protein deficiency ameliorates experimental autoimmune encephalomyelitis: the pathogenic role of lipocalin-2 in the central nervous system and peripheral lymphoid tissues. J Biol Chem. 2014; 289(24):16773-89. PMC: 4059121. DOI: 10.1074/jbc.M113.542282. View

Cowland J, Muta T, Borregaard N . IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta. J Immunol. 2006; 176(9):5559-66. DOI: 10.4049/jimmunol.176.9.5559. View

Abcouwer S, Lin C, Shanmugam S, Muthusamy A, Barber A, Antonetti D . Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury. J Neuroinflammation. 2013; 10:149. PMC: 3866619. DOI: 10.1186/1742-2094-10-149. View

10.

Tang W, Ma J, Gu R, Ding X, Lei B, Wang X . Lipocalin 2 Suppresses Ocular Inflammation by Inhibiting the Activation of NF-κβ Pathway in Endotoxin-Induced Uveitis. Cell Physiol Biochem. 2018; 46(1):375-388. DOI: 10.1159/000488472. View

11.

Choi Y, Jung K, Kim H, Chun J, Ahn M, Jee Y . Attenuation of Experimental Autoimmune Uveitis in Lewis Rats by Betaine. Exp Neurobiol. 2021; 30(4):308-317. PMC: 8424381. DOI: 10.5607/en21011. View

12.

Kjeldsen L, Johnsen A, Sengelov H, Borregaard N . Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993; 268(14):10425-32. View

13.

Agarwal R, Silver P, Caspi R . Rodent models of experimental autoimmune uveitis. Methods Mol Biol. 2012; 900:443-69. PMC: 3810964. DOI: 10.1007/978-1-60761-720-4_22. View

14.

Chun B, Kim J, Nam Y, Huh M, Han S, Suk K . Pathological Involvement of Astrocyte-Derived Lipocalin-2 in the Demyelinating Optic Neuritis. Invest Ophthalmol Vis Sci. 2015; 56(6):3691-8. DOI: 10.1167/iovs.15-16851. View

15.

Graca A, Hippert C, Pearson R . Müller Glia Reactivity and Development of Gliosis in Response to Pathological Conditions. Adv Exp Med Biol. 2018; 1074:303-308. DOI: 10.1007/978-3-319-75402-4_37. View

16.

Ghosh S, Shang P, Yazdankhah M, Bhutto I, Hose S, Montezuma S . Activating the AKT2-nuclear factor-κB-lipocalin-2 axis elicits an inflammatory response in age-related macular degeneration. J Pathol. 2016; 241(5):583-588. PMC: 5357190. DOI: 10.1002/path.4870. View

17.

Yoneshige A, Hagiyama M, Takashima Y, Ueno S, Inoue T, Kimura R . Elevated Hydrostatic Pressure Causes Retinal Degeneration Through Upregulating Lipocalin-2. Front Cell Dev Biol. 2021; 9:664327. PMC: 8201777. DOI: 10.3389/fcell.2021.664327. View

18.

Jang E, Lee S, Kim J, Kim J, Seo J, Lee W . Secreted protein lipocalin-2 promotes microglial M1 polarization. FASEB J. 2012; 27(3):1176-90. DOI: 10.1096/fj.12-222257. View

19.

Gao H, A L, Huang X, Chen X, Xu H . Müller Glia-Mediated Retinal Regeneration. Mol Neurobiol. 2021; 58(5):2342-2361. DOI: 10.1007/s12035-020-02274-w. View

20.

Behrens V, Voelz C, Muller N, Zhao W, Gasterich N, Clarner T . Lipocalin 2 as a Putative Modulator of Local Inflammatory Processes in the Spinal Cord and Component of Organ Cross talk After Spinal Cord Injury. Mol Neurobiol. 2021; 58(11):5907-5919. DOI: 10.1007/s12035-021-02530-7. View