Methods of inhibiting, protecting against, or treating uvr-induced skin damage

a technology of uvr and skin damage, applied in the direction of biochemistry apparatus and processes, instruments, drug compositions, etc., can solve the problems of dna crosslinking, single strand breakage, base pair loss, etc., and achieve the effect of reducing the level of syk kinas

Inactive Publication Date: 2017-04-13
DREXEL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach allows for the detection of UVR-induced skin damage, identification of at-risk individuals, and inhibition of UVR-induced skin damage, photoaging, or photocarcinogenesis by reducing Syk kinase levels in the skin, thereby treating associated diseases.

Problems solved by technology

However, the UVA and UVB generated free radicals such as OH radical, one-electron oxidation oxidants and single oxygen can still damage DNA and cause base pair loss, single strand breaks, and protein-DNA crosslinking (Ichibashi et al., 2003, Toxicology 189:21-39; Peus et al., 1998, J. Invest. Dermatol. 110:966-971; Darr et al., 1994, J. Invest. Dermatol. 102:671-675).

Method used

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  • Methods of inhibiting, protecting against, or treating uvr-induced skin damage
  • Methods of inhibiting, protecting against, or treating uvr-induced skin damage
  • Methods of inhibiting, protecting against, or treating uvr-induced skin damage

Examples

Experimental program
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Effect test

experimental example 1

Determination of UVA / UVB Dosage for Fibroblast Cells

[0347]Mouse fibroblast cells NIH3T3 (CRL-1658, ATCC) and Monkey kidney fibroblast cells COS-1 (CRL-1650, ATCC) were seeded into 4 cm tissue culture dishes in provided DMEM medium one day prior to UVR treatment. The cells were exposed to different dosages of UVR, provided by a Solar Stimulator (Abbott Laboratories, North Chicago, Ill.). The UVR dosages tested in these experiments were: 10 mJ / cm2, 25 mJ / cm2, 40 mJ / cm2, 50 mJ / cm2, and 75 mJ / cm2 (FIG. 2).

[0348]Fibroblast cell viability was evaluated 24 hours after UVR treatment using the trypan blue cell death assay. The data indicated that cell viability was significantly attenuated when the UVR dosage was increased from 50 mJ / cm2 to 75 mJ / cm2. Based on these data, a dosage of 60 mJ / cm2 for the UV radiation was selected for further study using Western blot assay analysis.

experimental example 2

Effects of UVA / UVB on the Expression of MMP-1 in Human Fibroblast

[0349]Human fibroblast cells (AG04058, Coriell) were grown in MEM completed medium. The fibroblast cells were plated into 4 cm tissue culture dishes the day before the assay. The fibroblast cells were treated with UVA or UVB at a dosage of 60 mJ / cm2 using a Stratalinker UV Crosslinker (Stratagene, La Jolla, Calif.). The supernatants from the cultures were collected at 6 hours and 24 hours after UV treatment. Cell viability was evaluated by trypan blue assay and found to be >95% at every indicated UV radiation dosage.

[0350]For the western blot, equal amounts of proteins were mixed with 2× sample buffer, boiled for 5 minutes, and chilled on ice. The samples were subjected to 4%-15% SDS-PAGE, and electrophoretically transferred to a nitrocellulose membrane. The membrane was blocked with 5% dry milk in washing buffer.

[0351]MMP-1 protein was detected with anti-MMP-1 antibody (Calbiochem). The result was visualized using the...

experimental example 3

Identification of Kinases Which Activity is Important for UV Induced Skin Damage

[0352]Human fibroblast cells (AG04058) were seeded into 24-well tissue culture dishes with MEM medium one day before the assay. Specific inhibitors for each kinase were added into each different well as indicated (FIG. 4). The supernatants were collected at 24 hours after UV treatment.

[0353]Protein samples from the cell supernatants were evaluated by western blot assay. The band of MMP-1 was observed in each treatment condition except in the presence of Syk kinase inhibitor. These data suggested that suppressing Syk with specific inhibitors suppressed MMP-1 expression (FIG. 4).

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Abstract

One aspect of the invention provides a method of inhibiting, protecting against, or treating UVR-induced skin damage in a mammal at risk of developing UVR-induced skin damage. The method includes the step of topically administering a pharmaceutical or cosmetic composition including an effective amount of a Syk kinase inhibitor to said mammal. The Syk kinase inhibitor inhibits the UVR-induced skin damage in the mammal. Another aspect of the invention provides a method of treating a disease or disorder associated with a change of Syk kinase expression in the skin in a mammal. The method includes the step of topically administering to said skin of said mammal a pharmaceutical or cosmetic composition including a therapeutically effective amount of at least one Syk kinase inhibitor, thereby reducing Syk kinase expression in the skin of the mammal and treating the disease or disorder.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application under 35 U.S.C. §§120 & 121 of U.S. patent application Ser. No. 13 / 575,559, having a 35 U.S.C. §371(c) completion date of Nov. 15, 2012, which is a national phase entry application under 35 U.S.C. §371 of PCT / US2011 / 024212, filed Feb. 9, 2011, which claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application Ser. No. 61 / 302,858, Feb. 9, 2010. The entire content of each of these applications is hereby incorporated by reference herein.BACKGROUND OF THE INVENTION[0002]Spleen tyrosine kinase (Syk) was originally cloned from porcine spleen (Taniguchi et al., 1991, J. Biol. Chem. 266:15790-15796). It was initially purified as a 40 kD protein-tyrosine kinase (PTK), but it was later found to be a major proteolytic product of a larger 72 kD mature protein (Taniguchi et al., 1991, J. Biol. Chem. 266:15790-15796; Law et al., 1994, J. Biol. Chem. 269:12310-12319; Zioncheck et al., 1986, ...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K8/34A61K9/127A61Q19/08A61K31/05A61K8/14A61Q17/04
CPCA61K8/347A61K8/14A61Q17/04A61K2800/782A61K31/05A61K9/127A61Q19/08G01N2333/912G01N2800/20G01N2800/40G01N33/573A61P35/00C12Q1/686
InventorPAPAZOGLOU, ELISABETH S.HUANG, ZHENYU
OwnerDREXEL UNIV