Activation of Skin Cells and Transcription Factors by S*
Activation of Skin Cells and Transcription Factors by S*
批准号:
6446077
负责人:
ROBERT A SWERLICK
金额:
$11.4万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-09-30 至 2002-09-29
中文摘要
刺激性皮炎是工作场所伤害的主要原因。它会影响
英文摘要
Irritant dermatitis is a major cause of workplace injury. It affects
individuals in a variety of work environments and is a source of
significant morbidity and lost work time. The pathophysiology of irritant
dermatitis is only poorly defined. Exposure of the skin to irritant chemicals
results in the rapid appearance of the cardinal features of inflammation
associated with cytokine activation and leukocyte infiltration. How irritants
activate inflammation is not known. We believe that irritants may activate
signaling pathways common to innate immune mechanisms. Centered in these
pathways are transcription factors that are linked to pro-inflammatory cytokine
genes, cell adhesion molecules, and proteins that trigger capillary leak. One
key family of transcription factors linked to the activation of these diverse
gene sets is the nuclear factor kappa B (NF-kB) family of transcription
factors. Our hypothesis is that irritant exposure results in NF-kB activation
in skin cells. This activation results in the triggering of a pro-inflammatory
cascade and the clinical appearance of dermatitis. In order to test this
hypothesis, we propose the following specific aims: 1) To examine whether
irritants can activate NF-kB in cultured skin cells in vitro using epithelial
and endothelial cells as targets. We will examine whether irritant treatment of
cultured skin cells results in translocation of active NF-kB complexes from the
cytoplasm to the nucleus; examine whether irritant treatment of HDMEC, HK, or
HDF induces the phosphorylation and ubiquitination of IkBa, necessary steps for
proteosome mediated degradation; examine whether translocated NF-kB complexes
are capable of binding to relevant response elements of cytokine and cell
adhesion molecule gene protomers. 2) To examine whether irritants can activate
specific genes in cultured skin cells in vitro using epithelial and endothelial
cells as targets. We will examine whether irritants induce or upregulate the
expression of adhesion molecules ICAM-1 and E-selectin, and proinflammatory
cytokines IL-8 and VEGF-C; examine whether irritants increase steady state mRNA
expression of ICAM-1, E-selectin, IL-8, or VEGF-C; examine whether irritant
treatment of cultured skin cells results in increase transcription of adhesion
molecule or cytokine genes dependent upon NF-kB responsive elements. These
studies will provide a framework to define the mechanisms by which irritants
cause inflammation in the skin and provide a rational and mechanistic targets
for prevention and treatment.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Irritant activation of epithelial cells is mediated via protease-dependent EGFR activation.
上皮细胞的刺激性激活是通过蛋白酶依赖性 EGFR 激活介导的。
DOI:
10.1038/jid.2010.308
发表时间:
2011
期刊:
The Journal of investigative dermatology
影响因子:
--
作者:
[White,KellieJ, Maffei,VincentJ, Newton-West,Marvin, Swerlick,RobertA]
通讯作者:
Swerlick,RobertA
CORE--MOLECULAR ANALYSIS
-
批准号:6645886
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2002
-
负责人:ROBERT A SWERLICK
-
依托单位:
Annual Dermatology Resident Retreat
-
批准号:8080852
-
项目类别:
-
资助金额:$1.5万
-
财政年份:2001
-
负责人:ROBERT A SWERLICK
-
依托单位:
Annual Dermatology Resident Retreat
-
批准号:7877814
-
项目类别:
-
资助金额:$1.5万
-
财政年份:2001
-
负责人:ROBERT A SWERLICK
-
依托单位:
Annual Dermatology Resident Retreat
-
批准号:7276522
-
项目类别:
-
资助金额:$1.5万
-
财政年份:2001
-
负责人:ROBERT A SWERLICK
-
依托单位:
CORE--MOLECULAR ANALYSIS
-
批准号:6459528
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2001
-
负责人:ROBERT A SWERLICK
-
依托单位:
Annual Dermatology Resident Retreat
-
批准号:7354746
-
项目类别:
-
资助金额:$1.5万
-
财政年份:2001
-
负责人:ROBERT A SWERLICK
-
依托单位:
Annual Dermatology Resident Retreat
-
批准号:7626348
-
项目类别:
-
资助金额:$1.5万
-
财政年份:2001
-
负责人:ROBERT A SWERLICK
-
依托单位:
Activation of Skin Cells and Transcription Factors by S*
-
批准号:6314892
-
项目类别:
-
资助金额:$11.47万
-
财政年份:2000
-
负责人:ROBERT A SWERLICK
-
依托单位:
CORE--MOLECULAR ANALYSIS
-
批准号:6324609
-
项目类别:
-
资助金额:$6.18万
-
财政年份:2000
-
负责人:ROBERT A SWERLICK
-
依托单位:
CORE--MOLECULAR ANALYSIS
-
批准号:6100611
-
项目类别:
-
资助金额:$6.87万
-
财政年份:1999
-
负责人:ROBERT A SWERLICK
-
依托单位:
CORE--MOLECULAR ANALYSIS
-
批准号:6268419
-
项目类别:
-
资助金额:$6.18万
-
财政年份:1998
-
负责人:ROBERT A SWERLICK
-
依托单位:
CORE--MOLECULAR ANALYSIS
-
批准号:6235812
-
项目类别:
-
资助金额:$5.56万
-
财政年份:1997
-
负责人:ROBERT A SWERLICK
-
依托单位:
EXPRESSION OF THE OX40/GP34 SYSTEM IN CUTANEOUS GRAFT VERSUS HOST DISEASE
-
批准号:6235808
-
项目类别:
-
资助金额:$5.56万
-
财政年份:1997
-
负责人:ROBERT A SWERLICK
-
依托单位:
NIAMS-Research Training in Dermatology
-
批准号:7242496
-
项目类别:
-
资助金额:$11.96万
-
财政年份:1994
-
负责人:ROBERT A SWERLICK
-
依托单位:
NIAMS-Research Training in Dermatology
-
批准号:7060950
-
项目类别:
-
资助金额:$18.9万
-
财政年份:1994
-
负责人:ROBERT A SWERLICK
-
依托单位:
NIAMS-Research Training in Dermatology
-
批准号:6749972
-
项目类别:
-
资助金额:$17.77万
-
财政年份:1994
-
负责人:ROBERT A SWERLICK
-
依托单位:
NIAMS-Research Training in Dermatology
-
批准号:6891930
-
项目类别:
-
资助金额:$15.4万
-
财政年份:1994
-
负责人:ROBERT A SWERLICK
-
依托单位:
NIAMS-Research Training in Dermatology
-
批准号:7436274
-
项目类别:
-
资助金额:$22.6万
-
财政年份:1994
-
负责人:ROBERT A SWERLICK
-
依托单位:
IMMORTALIZED HUMAN SKIN ENDOTHELIAL CELLS
-
批准号:2080791
-
项目类别:
-
资助金额:$17.89万
-
财政年份:1993
-
负责人:ROBERT A SWERLICK
-
依托单位:
VITRONECTIN RECEPTOR ON SKIN ENDOTHELIAL CELLS
-
批准号:2080938
-
项目类别:
-
资助金额:$11.38万
-
财政年份:1992
-
负责人:ROBERT A SWERLICK
-
依托单位:
海外基金