Protein kinase C-ζ mediates retinal degeneration in response to TNF

Liang, Hong; Baudouin, Christophe; Crisanti, Patricia; Omri, Boubaker

doi:10.1016/j.jneuroim.2006.11.028

Cited by 12 publications

(6 citation statements)

References 37 publications

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“…Concerted inhibition of adhesion complexes (see Additional File 3 , Supplement Figure S7B) is a likely explanation for the increased ONHA motility observed in glaucoma, and may contribute to a change in the physiological role of astroglia upon activation [ 3 , 48 ]. In good agreement with these findings, studies in an animal model of glaucoma also showed significant changes in the expression of ECM components [ 36 ], and a toxic decrease of PKC activity in retinal neurons [ 49 ]. However, results of individual studies on TGF- β , and PDGF activation in glaucoma [ 50 ] varied significantly, likely due to differences in the design, species and cellular populations examined.…”

Section: Resultssupporting

confidence: 53%

Network analysis of human glaucomatous optic nerve head astrocytes

Nikolskaya

Nikolsky²,

Serebryiskaya

et al. 2009

BMC Med Genomics

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Section: Resultssupporting

confidence: 53%

Network analysis of human glaucomatous optic nerve head astrocytes

Nikolskaya

Nikolsky²,

Serebryiskaya

et al. 2009

BMC Med Genomics

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“…But when TNF-α was injected in combination with a specific inhibitor of PKCζ, RGCs were exposed to TNF-α toxicity and significant RGC apoptosis was observed in the inner nuclear and ganglion cell layers. [48]…”

Section: Cell Signaling Mechanisms In Tnf-α Mediated Effects On Rgcsmentioning

confidence: 99%

Glaucomatous neurodegeneration: An eye on tumor necrosis factor-alpha

Agarwal

2012

Indian J Ophthalmol

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Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expression of tumor necrosis factor-α with glaucomatous neurodegeneraion, (2) Modulation of tumor necrosis factor-α expression by exposure to various risk factors of glaucoma, (3) Downstream cellular signaling mechanisms following interaction of tumor necrosis factor-α with its receptors and (4) Role of tumor necrosis factor-α as a possible target for therapeutic intervention in glaucoma. Literature was reviewed using PubMed search engine with relevant key words and a total of 82 English language papers published from 1990 to 2010 are included in this review.

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“…Therefore, the in-depth mechanisms of the effects of TNFα on keratinocytes are worthy of exploration. Previous studies have indicated that PKCζ is an important regulator of TNFα signaling via the NF-κB and MAPK signaling pathways in retinal endothelial cells and human umbilical vein endothelial cells ( 23 , 37 , 38 ); however, the function of PKCζ in human keratinocytes has not been fully investigated. Moreover, a previous study indicated that PKCζ expression was relatively increased and that it was involved in the upregulation of CD1d in the lesions of psoriasis, which is another chronic inflammatory skin disorder characterized by abnormal TNFα stimulation ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

PKCζ as a promising therapeutic target for TNFα-induced inflammatory disorders in chronic cutaneous wounds

Zhang¹,

Yang²,

Wang³

et al. 2017

International Journal of Molecular Medicine

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Protein kinase Cζ (PKCζ) is a member of the atypical protein kinase C family. Its roles in macrophages or skin-resident keratinocytes have not been fully evaluated. In this study, we provide evidence that PKCζ mediates lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) gene expression in the mouse macrophage cell line, RAW264.7. TNFα has been proven to be one of the main culprits of chronic wounds and impaired acute wounds, which are characterized by excessive inflammation, enhanced proteolysis and reduced matrix deposition. Among the multiple effects of TNFα on keratinocytes, the induction of chemokines which are indispensable factors involved in the massive infiltration of various inflammatory cells into skin lesions serves as a crucial mechanism. In the present study, we found that PKCζ inhibitor or its specific siRNA inhibited the TNFα-induced upregulation in the levels of the chemokines, interleukin (IL)-8, monocyte chemotactic protein-1 (MCP-1) and intercellular cell adhesion molecule-1 (ICAM-1) in HaCaT keratinocytes. Moreover, under a disrupted inflammatory environment, activated keratinocytes can synthesize large amounts of matrix metalloproteinases (MMP), which has a negative effect on tissue remodeling. We discovered that TNFα promoted the expression of MMP9 in a PKCζ-dependent manner. Further experiments revealed that nuclear factor-κB (NF-κB) was a key downstream molecule of PKCζ. In addition, as shown in vitro, PKCζ was not involved in the TNFα-induced decrease in HaCaT cell migration and proliferation. In vivo experiments demonstrated that TNFα-induced wound closure impairment and inflammatory disorders were significantly attenuated in the PKCζ inhibitor group. On the whole, our findings suggest that PKCζ is a crucial regulator in LPS- or TNFα-induced inflammatory responses in RAW264.7 cells and HaCaT keratinocytes, and that PKCζ/NF-κB signaling may be a potential target for interventional therapy for TNFα-induced skin inflammatory injury.

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Protein kinase C-ζ mediates retinal degeneration in response to TNF

Cited by 12 publications

References 37 publications

Network analysis of human glaucomatous optic nerve head astrocytes

Network analysis of human glaucomatous optic nerve head astrocytes

Glaucomatous neurodegeneration: An eye on tumor necrosis factor-alpha

PKCζ as a promising therapeutic target for TNFα-induced inflammatory disorders in chronic cutaneous wounds

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