Skip to main content
Log in

Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis

  • Original Article
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Atopic dermatitis (AD) is caused by both dysregulated immune responses and an impaired skin barrier. Although beta-galactoside-binding protein galectin-1 (Gal-1) has immunomodulatory effects in several inflammatory disorders, therapeutic strategies based on its anti-inflammatory properties have not been explored in AD. Thus, we evaluate pharmacological treatment with Gal-1 in the progression of an ovalbumin (OVA)-induced AD-like skin lesions. The skin of OVA-immunized male BALB/c mice was challenged with drops containing OVA on days 11, 14–18 and 21–24. Additionally, in the last week, a subset of animals was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). Treatment with rGal-1 decreased the clinical signs of dermatitis in BALB/c mice and diminished local eotaxin and IFN-γ levels. The treatment also suppressed the infiltration of eosinophils and mast cells, which was verified by reduced expression of mouse mast cell protease 6 (mMCP6) and eosinophil peroxidase (EPX). These localized effects are associated with extracellular signal-regulated kinase (ERK) activation and downregulation of endogenous Gal-1. The inhibition of disease progression induced by rGal-1 was also correlated with reduced plasma IL-17 levels. Our results demonstrate that rGal-1 is an effective treatment for allergic skin inflammation in AD and may impact the development of novel strategies for skin inflammatory diseases.

Key messages

  • Pharmacological treatment with rGal-1 reduces clinical signs of atopic dermatitis.

  • Systemic treatment with rGal-1 inhibits eosinophil and mast cell influx in the skin of AD animals.

  • rGal-1 reduced local eotaxin levels and systemic IL-17 levels.

  • The inhibition of disease progression induced by rGal-1 was correlated with upregulation of phosphorylated ERK.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Leung DY, Guttman-Yassky E (2014) Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J Allergy Clin Immunol 134:769–779

    Article  PubMed  PubMed Central  Google Scholar 

  2. Schlapbach C, Simon D (2014) Update on skin allergy. Allergy 69:1571–1581

    Article  CAS  PubMed  Google Scholar 

  3. Dhingra N, Gulati N, Guttman-Yassky E (2013) Mechanisms of contact sensitization offer insights into the role of barrier defects vs. intrinsic immune abnormalities as drivers of atopic dermatitis. J Invest Dermatol 133:2311–2314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. La M, Cao TV, Cerchiaro G, Chilton K, Hirabayashi J, Kasai K, Oliani SM, Chernajovsky Y, Perretti M (2003) A novel biological activity for galectin-1: inhibition of leukocyte-endothelial cell interactions in experimental inflammation. Am J Pathol 163:1505–1515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Norling LV, Sampaio AL, Cooper D, Perretti M (2008) Inhibitory control of endothelial galectin-1 on in vitro and in vivo lymphocyte trafficking. FASEB J 22:682–690

    Article  CAS  PubMed  Google Scholar 

  6. Gil CD, Cooper D, Rosignoli G, Perretti M, Oliani SM (2006) Inflammation-induced modulation of cellular galectin-1 and -3 expression in a model of rat peritonitis. Inflamm Res 55:99–107

    Article  CAS  PubMed  Google Scholar 

  7. Gil CD, Gullo CE, Oliani SM (2010) Effect of exogenous galectin-1 on leukocyte migration: modulation of cytokine levels and adhesion molecules. Int J Clin Exp Pathol 4:74–84

    PubMed  PubMed Central  Google Scholar 

  8. Cooper D, Norling LV, Perretti M (2008) Novel insights into the inhibitory effects of galectin-1 on neutrophil recruitment under flow. J Leukoc Biol 83:1459–1466

    Article  CAS  PubMed  Google Scholar 

  9. Mello CB, Ramos L, Gimenes AD, Andrade TR, Oliani SM, Gil CD (2015) Immunomodulatory effects of galectin-1 on an IgE-mediated allergic conjunctivitis model. Invest Ophthalmol Vis Sci 56:693–704

    Article  CAS  PubMed  Google Scholar 

  10. Hsieh SH, Ying NW, Wu MH, Chiang WF, Hsu CL, Wong TY, Jin YT, Hong TM, Chen YL (2008) Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene 27:3746–3753

    Article  CAS  PubMed  Google Scholar 

  11. Auvynet C, Moreno S, Melchy E, Coronado-Martínez I, Montiel JL, Aguilar-Delfin I, Rosenstein Y (2013) Galectin-1 promotes human neutrophil migration. Glycobiology 23:32–42

    Article  CAS  PubMed  Google Scholar 

  12. Arthur JS, Ley SC (2013) Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol 13:679–692

    Article  CAS  PubMed  Google Scholar 

  13. Pelaia G, Cuda G, Vatrella A, Gallelli L, Caraglia M, Marra M, Abbruzzese A, Caputi M, Maselli R, Costanzo FS et al (2005) Mitogen-activated protein kinases and asthma. J Cell Physiol 202:642–653

    Article  CAS  PubMed  Google Scholar 

  14. Acciani TH, Suzuki T, Trapnell BC, Le Cras TD (2016) Epidermal growth factor receptor signalling regulates granulocyte-macrophage colony-stimulating factor production by airway epithelial cells and established allergic airway disease. Clin Exp Allergy 46:317–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kim H, Kim JR, Kang H, Choi J, Yang H, Lee P, Kim J, Lee KW (2014) 7,8,4′-Trihydroxyisoflavone attenuates DNCB-induced atopic dermatitis-like symptoms in NC/Nga mice. PLoS One 9:e104938

    Article  PubMed  PubMed Central  Google Scholar 

  16. Akimoto Y, Hirabayashi J, Kasai K, Hirano H (1995) Expression of the endogenous 14-kDa beta-galactoside-binding lectin galectin in normal human skin. Cell Tissue Res 280:1–10

    Article  CAS  PubMed  Google Scholar 

  17. Klíma J, Lacina L, Dvoránková B, Herrmann D, Carnwath JW, Niemann H, Kaltner H, André S, Motlík J, Gabius HJ et al (2009) Differential regulation of galectin expression/reactivity during wound healing in porcine skin and in cultures of epidermal cells with functional impact on migration. Physiol Res 58:873–884

    PubMed  Google Scholar 

  18. Kim HJ, Kim YJ, Kang MJ, Seo JH, Kim HY, Jeong SK, Lee SH, Kim JM, Hong SJ (2012) A novel mouse model of atopic dermatitis with epicutaneous allergen sensitization and the effect of Lactobacillus rhamnosus. Exp Dermatol 21:672–675

    Article  CAS  PubMed  Google Scholar 

  19. Heo WI, Lee KE, Hong JY, Kim MN, Oh MS, Kim YS, Kim KW, Kim KE, Sohn MH (2015) The role of interleukin-17 in mouse models of atopic dermatitis and contact dermatitis. Clin Exp Dermatol 40:665–671

    Article  CAS  PubMed  Google Scholar 

  20. Ma L, Xue HB, Guan XH, Shu CM, Wang F, Zhang JH, An RZ (2014) The imbalance of Th17 cells and CD4(+) CD25(high) Foxp3(+) Treg cells in patients with atopic dermatitis. J Eur Acad Dermatol Venereol 28:1079–1086

    Article  CAS  PubMed  Google Scholar 

  21. Leonardi S, Cuppari C, Manti S, Filippelli M, Parisi GF, Borgia F, Briuglia S, Cannavò P, Salpietro A, Arrigo T et al (2015) Serum interleukin 17, interleukin 23, and interleukin 10 values in children with atopic eczema/dermatitis syndrome (AEDS): association with clinical severity and phenotype. Allergy Asthma Proc 36:74–81

    Article  CAS  PubMed  Google Scholar 

  22. Shershakova N, Bashkatova E, Babakhin A, Andreev S, Nikonova A, Shilovsky I, Kamyshnikov O, Buzuk A, Elisyutina O, Fedenko E et al (2015) Allergen-specific immunotherapy with monomeric allergoid in a mouse model of atopic dermatitis. PLoS One 10:e0135070

    Article  PubMed  PubMed Central  Google Scholar 

  23. Nakajima S, Kitoh A, Egawa G, Natsuaki Y, Nakamizo S, Moniaga CS, Otsuka A, Honda T, Hanakawa S, Amano W et al (2014) IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models. J Invest Dermatol 134:2122–2130

    Article  CAS  PubMed  Google Scholar 

  24. Cedeno-Laurent F, Barthel SR, Opperman MJ, Lee DM, Clark RA, Dimitroff CJ (2010) Development of a nascent galectin-1 chimeric molecule for studying the role of leukocyte galectin-1 ligands and immune disease modulation. J Immunol 185:4659–4672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Iqbal AJ, Cooper D, Vugler A, Gittens BR, Moore A, Perretti M (2013) Endogenous galectin-1 exerts tonic inhibition on experimental arthritis. J Immunol 191:171–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Juszczynski P, Ouyang J, Monti S, Rodig SJ, Takeyama K, Abramson J, Chen W, Kutok JL, Rabinovich GA, Shipp MA (2007) The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A 104:13134–13139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yakushina VD, Vasil'eva OA, Ryazantseva NV, Novitsky VV, Tashireva LA (2015) The effects of galectin-1 on the gene expression of the transcription factors TBX21, GATA-3, FOXP3 and RORC. Mol Cell Biochem 398:245–249

    Article  CAS  PubMed  Google Scholar 

  28. Rabinovich GA, Daly G, Dreja H, Tailor H, Riera CM, Hirabayashi J, Chernajovsky Y (1999) Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis. J Exp Med 190:385–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Santucci L, Fiorucci S, Rubinstein N, Mencarelli A, Palazzetti B, Federici B, Rabinovich GA, Morelli A (2003) Galectin-1 suppresses experimental colitis in mice. Gastroenterology 124:1381–1394

    Article  CAS  PubMed  Google Scholar 

  30. Toscano MA, Commodaro AG, Ilarregui JM, Bianco GA, Liberman A, Serra HM, Hirabayashi J, Rizzo LV, Rabinovich GA (2006) Galectin-1 suppresses autoimmune retinal disease by promoting concomitant Th2- and T regulatory-mediated anti-inflammatory responses. J Immunol 176:6323–6332

    Article  CAS  PubMed  Google Scholar 

  31. de la Fuente H, Perez-Gala S, Bonay P, Cruz-Adalia A, Cibrian D, Sanchez-Cuellar S, Dauden E, Fresno M, García-Diez A, Sanchez-Madrid F (2012) Psoriasis in humans is associated with down-regulation of galectins in dendritic cells. J Pathol 228:193–203

    Article  PubMed  Google Scholar 

  32. Yu M, Eckart MR, Morgan AA, Mukai K, Butte AJ, Tsai M, Galli SJ (2011) Identification of an IFN-γ/mast cell axis in a mouse model of chronic asthma. J Clin Invest 121:3133–3143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ge XN, Ha SG, Greenberg YG, Rao A, Bastan I, Blidner AG, Rao SP, Rabinovich GA, Sriramarao P (2016) Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1. Proc Natl Acad Sci U S A 113:E4837–E4846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Delbrouck C, Doyen I, Belot N, Decaestecker C, Ghanooni R, de Lavareille A, Kaltner H, Choufani G, Danguy A, Vandenhoven G et al (2002) Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration. Lab Investig 82:147–158

    Article  CAS  PubMed  Google Scholar 

  35. Vespa GN, Lewis LA, Kozak KR, Moran M, Nguyen JT, Baum LG, Miceli MC (1999) Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation. J Immunol 162:799–806

    CAS  PubMed  Google Scholar 

  36. Barrionuevo P, Beigier-Bompadre M, Ilarregui JM, Toscano MA, Bianco GA, Isturiz MA, Rabinovich GA (2007) A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway. J Immunol 178:436–445

    Article  CAS  PubMed  Google Scholar 

  37. Muglia CI, Gobbi RP, Smaldini P, Delgado ML, Candia M, Zanuzzi C, Sambuelli A, Rocca A, Toscano MA, Rabinovich GA et al (2016) Inflammation controls sensitivity of human and mouse intestinal epithelial cells to galectin-1. J Cell Physiol 231:1575–1585

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP - 2015/09858-3). MP Correa was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cristiane Damas Gil.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Corrêa, M.P., Andrade, F.E.C., Gimenes, A.D. et al. Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis. J Mol Med 95, 1005–1015 (2017). https://doi.org/10.1007/s00109-017-1566-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-017-1566-9

Keywords

Navigation