Resident Corneal Cells Communicate with Neutrophils Leading to the Production of IP-10 during the Primary Inflammatory Response to HSV-1 Infection

Molesworth-Kenyon, S. J.; Popham, N.; Milam, Ashley A. Viehmann; Oakes, John E.; Lausch, Robert N.

doi:10.1155/2012/810359

Cited by 14 publications

(6 citation statements)

References 39 publications

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“…Few reports have used immunofluorescence staining to investigate the cells expressing CXCL10 in the HSV-1-infected cornea in vivo (18,31,43). In this study, we detected abundant CXCL10 in epithelial cells.…”

Section: Discussionmentioning

confidence: 62%

Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice

Shen

Wang

Yeh

et al. 2013

J Virol

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Section: Discussionmentioning

confidence: 62%

Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice

Shen

Wang

Yeh

et al. 2013

J Virol

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“…Next, we investigated the effects of inhibition of NKO on expression of inflammatory cytokines (IL-6, IL-10, INFγ, IP10, TNFα and IL-12), upon LPS-induced NFκB activation. The NKO group showed reduced expression of various pro-inflammatory cytokines (IL617, IP1018 and TNFα19) compared with the NWT group (Fig. 8Ci and ii).…”

Section: Resultsmentioning

confidence: 95%

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

Poon

Jiang

Qin

et al. 2017

Sci Rep

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Corneal wound healing involves a complex cascade of cytokine-controlled cellular events, including inflammatory and angiogenesis responses that are regulated by transcriptional chromatin remodeling. Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate (NUCKS) is a key chromatin modifier and transcriptional regulator of metabolic signaling. In this study, we investigated the role of NUCKS in corneal wound healing by comparing its effects on corneal alkali burn in NUCKS knockout (NKO) and NUCKS wild-type (NWT) mice. Our data showed that following alkali-injury, inhibition of NUCKS (NKO) accelerated ocular resurfacing and suppressed neovascularization; the cytokine profile of alkali burned corneas in NKO mice showed suppressed expression of inflammation cytokines (IL1A & IL1B); upregulated expression of antiangiogenic factor (Pigment Epithelium-derived Factor; PEDF); and downregulated expression of angiogenic factor (Vascular Endothelial Growth Factor, VEGF); in vitro, following LPS-induced NFκB activation, NKO corneal cells showed reduced expression of IL6, IP10 and TNFα. In vitro, corneal epithelial cells showed reduced NF-κb activation on silencing of NUCKS and corresponding NFκB-mediated cytokine expression was reduced. Here, we illustrate that inhibition of NUCKS played a role in cytokine modulation and facilitated corneal recovery. This reveals a potential new effective strategy for ocular burn treatment.

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“…Another important function of PMN is the production of soluble immune mediators, including AMP and other chemokines that could contribute to the HSV-resistant environment induced following IL-36γ treatment. An important chemokine produced by PMN is IP-10, a T-cell chemoattractant that contributes to controlling HSV replication in vivo [70–72]. We measured elevated levels of IP-10 (5-fold) in vaginal lavages 4h after IL-36γ treatment, that corresponded with increased CCL20 and KC levels at the same time point (Fig.…”

Section: Discussionmentioning

confidence: 99%

IL-36γ induces a transient HSV-2 resistant environment that protects against genital disease and pathogenesis

Gardner

Herbst-Kralovetz

2018

Cytokine

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Herpes simplex virus 2 (HSV-2) causes a persistent, lifelong infection that increases risk for sexually transmitted infection acquisition. Both the lack of a vaccine and the need for chronic suppressive therapies to control infection presents the need to further understand immune mechanisms in response to acute HSV-2 infection. The IL-36 cytokines are recently identified members of the IL-1 family and function as inflammatory mediators at epithelial sites. Here, we first used a well-characterized three-dimensional (3-D) human vaginal epithelial cell (VEC) model to understand the role of IL-36γ in the context of HSV-2 infection. In 3-D VEC, IL-36γ is induced by HSV-2 infection, and pretreatment with exogenous IL-36γ significantly reduced HSV-2 replication. To assess the impact of IL-36γ treatment on HSV-2 disease pathogenesis, we employed a lethal genital infection model. We showed that IL-36γ treatment in mice prior to lethal intravaginal challenge significantly limited vaginal viral replication, delayed disease onset, decreased disease severity, and significantly increased survival. We demonstrated that IL-36γ treatment transiently induced pro-inflammatory cytokines, chemokines, and antimicrobial peptides in murine lower female reproductive tract (FRT) tissue and vaginal lavages. Induction of the chemokines CCL20 and KC in IL-36γ treated mice also corresponded with increased polymorphonuclear (PMN) leukocyte infiltration observed in vaginal smears. Altogether, these studies demonstrate that IL-36γ drives the transient production of immune mediators and promotes PMN recruitment in the vaginal microenvironment that increases resistance to HSV-2 infection and disease. Our data indicate that IL-36γ may participate as a key player in host defense mechanisms against invading pathogens in the FRT.

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Resident Corneal Cells Communicate with Neutrophils Leading to the Production of IP-10 during the Primary Inflammatory Response to HSV-1 Infection

Cited by 14 publications

References 39 publications

Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice

Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

IL-36γ induces a transient HSV-2 resistant environment that protects against genital disease and pathogenesis

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