Expression of Th-1 Chemokines and Chemokine Receptors on the Ocular Surface of C57BL/6 Mice: Effects of Desiccating Stress

Yoon, Kyung-Chul; Paiva, Cintia S. de; Qi, Hong; Chen, Zhuo; Farley, William J.; Li, Dequan; Pflugfelder, Stephen C.

doi:10.1167/iovs.07-0002

Cited by 152 publications

(147 citation statements)

References 38 publications

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“…28 Autoreactive CD4 þ T cells are recruited to the ocular surface by chemokines such as CCL2, CCL5, and CXCL9-11, leading to immune-mediated ocular surface damage. 7,25 TLR4 ligation results in the production of proinflammatory cytokines such as IL-1b, IL-6, and TNF that promote the activation of leukocytes and lymphocytes. 10,29 TLR4 signaling is important for the activation of APC-and T-cell-mediated immunoinflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

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Expression of Toll-Like Receptor 4 Contributes to Corneal Inflammation in Experimental Dry Eye Disease

Lee¹,

Hattori²,

Park³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the corneal expression of toll-like receptor (TLR) 4 and determine its contribution to the immunopathogenesis of dry eye disease (DED).METHODS. Seven to 8-week-old female C57BL/6 mice were housed in a controlled environment chamber and administered scopolamine to induce experimental DED. Mice received intravenous TLR4 inhibitor (Eritoran) to block systemic TLR4-mediated activity. The expression of TLR4 by the corneal epithelium and stroma was evaluated using real-time polymerase chain reaction and flow cytometry. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease severity. The corneal expression of proinflammatory cytokines (IL-1b, IL-6, TNF, and CCL2), corneal infiltration of CD11b 3 Recent studies have demonstrated that corneal epithelial cells respond to hyperosmolar stress by producing proinflammatory cytokines, chemokines, and matrix metalloproteinases (MMPs).4,5 Furthermore, hyperosmolar stress and proinflammatory cytokines such as interferon (IFN)-c promote epithelial cell apoptosis. [5][6][7][8] Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system that recognize highly conserved microbial structures and products.9,10 To date, 12 murine TLRs have been identified, and TLRs are expressed by a variety of cell types, including epithelial cells, dendritic cells, macrophages, and lymphocytes.10-13 TLR stimulation leads to the activation of nuclear factor-kappaB (NF-jB) that upregulates the production of proinflammatory cytokines and antimicrobial proteins.10,14 The NF-jB signaling pathway is important for the induction of innate and adaptive immune responses. 10,14 TLR4 recognizes the Gram-negative bacterial cell wall component lipopolysaccharide (LPS) in association with cofactors such as CD14, LPS-binding protein (LBP), and myeloid differentiation factor-2 (MD-2). 15,16 It has also been suggested that TLR4 is a receptor for endogenous ligands associated with noninfectious diseases such as myocardial ischemia-reperfusion injury and central nervous system autoimmune disease. 17,18 We hypothesized that DED-induced corneal inflammation and injury may lead to the production of endogenous TLR4 ligands that activate the immune system. Therefore, we investigated the corneal expression of TLR4 and sought to determine the expression pattern of TLR4 in DED. MATERIALS AND METHODS AnimalsSeven to 8-week-old female C57BL/6 mice (Charles River Laboratories, Wilmington, MA) were used for these experiments. The experimental protocol was approved by the Institutional Animal Care and Use Committee, and all animals were managed according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Dry Eye ModelDED was induced by placing mice in a controlled environment chamber (CEC) and administering scopolamine (Sigma-Aldrich, St. Louis, MO) to maximize ocular surface dryness, as previously described. 19,20 Mice placed in the CEC were exposed to a relative humidity < 25%, temperature of 20 to 228C, and airflow of 15 L/min, 2...

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Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system that recognize highly conserved microbial structures and products.…”

Section: Purposementioning

confidence: 99%

Expression of Toll-Like Receptor 4 Contributes to Corneal Inflammation in Experimental Dry Eye Disease

Lee¹,

Hattori²,

Park³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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“…33 To investigate the possibility that ICAM-1 is necessary for expression of chemokines that attract ␥␦ T cells, we assessed epithelial mRNA levels for an array of chemokines reported to be chemotactic for ␥␦ T cells. Limbal and paralimbal epithelium (ie, the regions not directly injured during abrasion) was collected from wild-type and ICAM-1 Ϫ/Ϫ mice, either uninjured or 3 hours after central epithelial abrasion.…”

Section: Icam-1 and Chemokine Expression By Corneal Epitheliummentioning

confidence: 99%

ICAM-1 Is Necessary for Epithelial Recruitment of γδ T Cells and Efficient Corneal Wound Healing

Byeseda

Burns

Dieffenbaugher

et al. 2009

The American Journal of Pathology

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Wound healing and inflammation are both significantly reduced in mice that lack ␥␦ T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in ␥␦ T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epithelial ␥␦ T cells at 24 hours after epithelial abrasion. ICAM-1 ؊/؊ mice had 50.9% (P < 0.01) fewer ␥␦ T cells resident in unwounded corneal epithelium, which failed to increase in response to epithelial abrasion. Anti-ICAM-1 blocking antibody in wild-type mice reduced epithelial ␥␦ T cells to a number comparable to that of ICAM-1 ؊/؊ mice, and mice deficient in lymphocyte function-associated antigen-1 (CD11a/CD18), a principal leukocyte receptor for ICAM-1, exhibited a 48% reduction (P < 0.01) in peak epithelial ␥␦ T cells. Re-epithelialization and epithelial cell division were both significantly reduced (ϳ50% at 18 hours, P < 0.01) after abrasion in ICAM-1 ؊/؊ mice versus wildtype, and at 96 hours, recovery of epithelial thickness was only 66% (P < 0.01) of wild-type. ICAM-1 expression by corneal epithelium in response to epithelial abrasion appears to be critical for accumulation of ␥␦ T cells in the epithelium , and deficiency of ICAM-1 significantly delays wound healing. Since ␥␦ T cells are necessary for efficient epithelial wound healing , ICAM-1 may contribute to wound healing by facilitating ␥␦ T cell migration into the corneal epithelium.

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“…After activation, Th cells can differentiate into Th-1, Th-2, Th-3, and Th-17 subtypes. Studies have shown that Th-1 and Th-17 cells are correlated with the pathogenesis of dry eye (Stern et al, 2005;Yoon et al, 2007;De Paiva et al, 2009;El Annan et al, 2009;Zheng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye

Hsu¹,

Lee²,

Chang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL-6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TOrelated dry eye or other ocular surface inflammatory disorders.

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Expression of Th-1 Chemokines and Chemokine Receptors on the Ocular Surface of C57BL/6 Mice: Effects of Desiccating Stress

Cited by 152 publications

References 38 publications

Expression of Toll-Like Receptor 4 Contributes to Corneal Inflammation in Experimental Dry Eye Disease

Expression of Toll-Like Receptor 4 Contributes to Corneal Inflammation in Experimental Dry Eye Disease

ICAM-1 Is Necessary for Epithelial Recruitment of γδ T Cells and Efficient Corneal Wound Healing

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye

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