Intercellular Adhesion Molecule-1 Deficiency Attenuates the Development of Skin Fibrosis in Tight-Skin Mice

Matsushita, Yukiyo; Hasegawa, Minoru; Matsushita, T.; Fujimoto, Manabu; Horikawa, Mayuka; Fujita, Tomoyuki; Kawasuji, Ayako; Ogawa, Fumihide; Steeber, Douglas A.; Tedder, Thomas F.; Takehara, Kazuhiko; Sato, Shinichi

doi:10.4049/jimmunol.179.1.698

Cited by 34 publications

(39 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By contrast, allergic lung disease is reduced in mice deficient for LFA-1, an ICAM-1 counterreceptor, which is due to markedly impaired recruitment of Th2 cells to the lungs (Lee et al , 2008). Similarly, ICAM-1 deficiency attenuates skin fibrosis and leukocyte infiltration with decreased Th2 cytokine expression in the affected skin from tight-skin mouse, a model of systemic sclerosis (Matsushita et al , 2007). On the other hand, in experimental autoimmune uveoretinnitis, trafficking of both Th1 and Th2 cells across the blood-retina barrier is mediated by ICAM-1 and LFA-1 interaction (Xu et al , 2004).…”

Section: Discussionmentioning

confidence: 99%

The Differential Role of L-Selectin and ICAM-1 in Th1-Type and Th2-Type Contact Hypersensitivity

Ogawa

Yoshizaki

Yanaba

et al. 2010

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

Sensitization and challenge using dinitrofluorobenzene (DNFB) induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, while those using fluorescein isothiocyanate (FITC) generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process highly regulated by expression of multiple adhesion molecules. To determine a role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in Th1- and Th2-type CHS, CHS induced by DNFB or FITC in mice lacking L-selectin, ICAM-1 (ICAM-1−/−), or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-γ expression. Similarly, Th2-type CHS was induced by FITC was inhibited by L-selectin deficiency. In contrast, Th2-type CHS was increased by ICAM-1 deficiency, which was accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1−/− mice, while in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased and relatively Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS.

show abstract

Section: Discussionmentioning

confidence: 99%

The Differential Role of L-Selectin and ICAM-1 in Th1-Type and Th2-Type Contact Hypersensitivity

Ogawa

Yoshizaki

Yanaba

et al. 2010

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…ICAM-1 −/− , P-selectin −/− , E-selectin −/− , and PSGL-1 −/− mice were obtained from The Jackson Laboratory (Bar Harbor, ME). Mice lacking both L-selectin and ICAM-1 (L-selectin/ICAM-1 −/− ) were generated as described previously (18). All mice were backcrossed 10 generations onto the C57BL/6 genetic background.…”

Section: Methodsmentioning

confidence: 99%

Cell Adhesion Molecules Regulate Fibrotic Process via Th1/Th2/Th17 Cell Balance in a Bleomycin-Induced Scleroderma Model

Yoshizaki

Yanaba

Iwata

et al. 2010

The Journal of Immunology

Self Cite

126

View full text Add to dashboard Cite

Mice subcutaneously injected with bleomycin, an experimental model for human systemic sclerosis, develop skin and lung fibrosis, which is mediated by inflammatory cell infiltration. This process is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules in this pathogenetic process, the bleomycin-induced fibrosis was examined in mice lacking adhesion molecules. In addition, this model does not require antigen sensitization. Therefore, we can exclude the possible role of adhesion molecules on the sensitization phase. L-selectin and/or ICAM-1 deficiency inhibited skin and lung fibrosis with decreased Th2 and Th17 cytokines and increased Th1 cytokines. By contrast, P-selectin deficiency, E-selectin deficiency with or without P-selectin blockade, or PSGL-1 deficiency augmented the fibrosis in parallel with increased Th2 and Th17 cytokines and decreased Th1 cytokines. Furthermore, loss of L-selectin and/or ICAM-1 reduced Th2 and Th17 cell numbers in bronchoalveolar lavage fluid, whereas loss of P-selectin, E-selectin, or PSGL-1 reduced Th1 cell numbers. Moreover, Th1 cells exhibited higher PSGL-1 expression and lower expression of LFA-1, a ligand for ICAM-1, while Th2 and Th17 cells showed higher LFA-1 and lower PSGL-1 expression. This study suggests that L-selectin and ICAM-1 regulate Th2 and Th17 cell accumulation into the skin and lung, leading to the development of fibrosis, and that P-selectin, E-selectin, and PSGL-1 regulate Th1 cell infiltration, resulting in the inhibition of fibrosis.

show abstract

“…ICAM-1, an inducible surface glycoprotein that promotes adhesion in immunologic and inflammatory reactions, plays a role in a variety of inflammatory and neoplastic diseases. ICAM-1 also contributes significantly to the development of skin fibrosis, especially via ICAM-1 expression in skin fibroblasts (19).…”

Section: Hdac-7 As a Target For Antifibrotic Therapy For Sscmentioning

confidence: 99%

Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis

Hemmatazad¹,

Rodrigues²,

Maurer³

et al. 2009

Arthritis & Rheumatism

102

View full text Add to dashboard Cite

Objective. We have recently shown a significant reduction in cytokine-induced transcription of type I collagen and fibronectin in systemic sclerosis (SSc) skin fibroblasts upon treatment with trichostatin A (TSA). Moreover, in a mouse model of fibrosis, TSA prevented the dermal accumulation of extracellular matrix. The purpose of this study was to analyze the silencing of histone deacetylase 7 (HDAC-7) as a possible mechanism by which TSA exerts its antifibrotic function.Methods. Skin fibroblasts from patients with SSc were treated with TSA and/or transforming growth factor ␤. Expression of HDACs 1-11, extracellular matrix proteins, connective tissue growth factor (CTGF), and intercellular adhesion molecule 1 (ICAM-1) was analyzed by real-time polymerase chain reaction, Western blotting, and the Sircol collagen assay. HDAC-7 was silenced using small interfering RNA.Results. SSc fibroblasts did not show a specific pattern of expression of HDACs. TSA significantly inhibited the expression of HDAC-7, whereas HDAC-3 was up-regulated. Silencing of HDAC-7 decreased the constitutive and cytokine-induced production of type I and type III collagen, but not fibronectin, as TSA had done. Most interestingly, TSA induced the expression of CTGF and ICAM-1, while silencing of HDAC-7 had no effect on their expression.Conclusion. Silencing of HDAC-7 appears to be not only as effective as TSA, but also a more specific target for the treatment of SSc, because it does not up-regulate the expression of profibrotic molecules such as ICAM-1 and CTGF. This observation may lead to the development of more specific and less toxic targeted therapies for SSc.

show abstract

Intercellular Adhesion Molecule-1 Deficiency Attenuates the Development of Skin Fibrosis in Tight-Skin Mice

Cited by 34 publications

References 60 publications

The Differential Role of L-Selectin and ICAM-1 in Th1-Type and Th2-Type Contact Hypersensitivity

The Differential Role of L-Selectin and ICAM-1 in Th1-Type and Th2-Type Contact Hypersensitivity

Cell Adhesion Molecules Regulate Fibrotic Process via Th1/Th2/Th17 Cell Balance in a Bleomycin-Induced Scleroderma Model

Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis

Contact Info

Product

Resources

About