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Evaluation of apoptosis regulatory proteins in response to PUVA therapy for psoriasis
Summary Background The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. One of the actions of psoralen ultraviolet A (PUVA) in psoriasis could be exerted through induction of apoptosis of keratinocytes and lymphocytes; however, its exact molecular mechani...
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| Published in: | Photodermatology, photoimmunology & photomedicine photoimmunology & photomedicine, 2013-02, Vol.29 (1), p.18-26 |
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| container_title | Photodermatology, photoimmunology & photomedicine |
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| creator | El-Domyati, Moetaz Moftah, Noha H. Nasif, Ghada A. Abdel-Wahab, Hossam M. Barakat, Manal T. Abdel-Aziz, Rasha T. |
| description | Summary
Background
The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. One of the actions of psoralen ultraviolet A (PUVA) in psoriasis could be exerted through induction of apoptosis of keratinocytes and lymphocytes; however, its exact molecular mechanism is still confusing.
Aim
In this study, we evaluated the expression of pro‐apoptotic (P53, Fas and Bax) and anti‐apoptotic (Bcl‐2) proteins correlating it with apoptotic index (AI) and epidermal thickness in psoriatic skin before and after PUVA therapy.
Methods
Lesional and non‐lesional skin biopsy specimens were obtained from 10 patients with generalized plaque psoriasis before and after 8 weeks of PUVA therapy. Histometric measurements of epidermal thickness as well as P53, Fas, Bax and Bcl‐2 expressions were evaluated using immunoperoxidase technique and apoptotic cells were detected by terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method.
Results
After PUVA therapy, the epidermal thickness of psoriatic skin was significantly decreased (P |
| doi_str_mv | 10.1111/phpp.12012 |
| format | article |
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Background
The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. One of the actions of psoralen ultraviolet A (PUVA) in psoriasis could be exerted through induction of apoptosis of keratinocytes and lymphocytes; however, its exact molecular mechanism is still confusing.
Aim
In this study, we evaluated the expression of pro‐apoptotic (P53, Fas and Bax) and anti‐apoptotic (Bcl‐2) proteins correlating it with apoptotic index (AI) and epidermal thickness in psoriatic skin before and after PUVA therapy.
Methods
Lesional and non‐lesional skin biopsy specimens were obtained from 10 patients with generalized plaque psoriasis before and after 8 weeks of PUVA therapy. Histometric measurements of epidermal thickness as well as P53, Fas, Bax and Bcl‐2 expressions were evaluated using immunoperoxidase technique and apoptotic cells were detected by terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method.
Results
After PUVA therapy, the epidermal thickness of psoriatic skin was significantly decreased (P < 0.001) and keratinocytes of psoriatic skin showed significant increased expression of P53 (P < 0.001), Fas (P < 0.001) and Bcl‐2 (P < 0.001) with no significant change in Bax expression (P > 0.05). Apart from significant decrease of Bcl‐2 expression (P = 0.01), no significant difference in all previous markers were encountered in lymphocytes (P53, Fas and Bax; P > 0.05) after PUVA therapy. The AI was significantly increased (P = 0.008) after PUVA therapy especially in lymphocytes (P = 0.002).
Conclusion
The present study suggests that one of the actions of PUVA therapy in psoriasis might be exerted through induction of apoptosis especially of lymphocytes by suppression of Bcl‐2 expression and of keratinocytes through P53 and Fas pathways leading to healing of psoriasis.</description><identifier>ISSN: 0905-4383</identifier><identifier>EISSN: 1600-0781</identifier><identifier>DOI: 10.1111/phpp.12012</identifier><identifier>PMID: 23281693</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing Ltd</publisher><subject>Adult ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - radiation effects ; Apoptosis Regulatory Proteins - biosynthesis ; Bax protein ; Bcl-2 ; Bcl-2 protein ; Biological and medical sciences ; Biopsy ; CD95 antigen ; Dermatology ; DNA nucleotidylexotransferase ; Fas antigen ; Female ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - radiation effects ; Humans ; Keratinocytes ; Keratinocytes - metabolism ; Keratinocytes - pathology ; Lymphocytes ; Male ; Medical sciences ; Middle Aged ; Molecular modelling ; P53 ; p53 protein ; Plaques ; psoralen ; Psoriasis ; Psoriasis - drug therapy ; Psoriasis - metabolism ; Psoriasis - pathology ; Psoriasis. Parapsoriasis. Lichen ; PUVA ; PUVA Therapy ; regulatory proteins ; Skin ; Skin diseases ; Time Factors ; U.V. radiation</subject><ispartof>Photodermatology, photoimmunology & photomedicine, 2013-02, Vol.29 (1), p.18-26</ispartof><rights>2013 John Wiley & Sons A/S</rights><rights>2014 INIST-CNRS</rights><rights>2013 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4302-d28c9c4ab26a8d7e354b26778a42eab60282d967abe2987ded89f8942c0f537d3</citedby><cites>FETCH-LOGICAL-c4302-d28c9c4ab26a8d7e354b26778a42eab60282d967abe2987ded89f8942c0f537d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26780666$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23281693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El-Domyati, Moetaz</creatorcontrib><creatorcontrib>Moftah, Noha H.</creatorcontrib><creatorcontrib>Nasif, Ghada A.</creatorcontrib><creatorcontrib>Abdel-Wahab, Hossam M.</creatorcontrib><creatorcontrib>Barakat, Manal T.</creatorcontrib><creatorcontrib>Abdel-Aziz, Rasha T.</creatorcontrib><title>Evaluation of apoptosis regulatory proteins in response to PUVA therapy for psoriasis</title><title>Photodermatology, photoimmunology & photomedicine</title><addtitle>Photodermatol. Photoimmunol. Photomed</addtitle><description>Summary
Background
The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. One of the actions of psoralen ultraviolet A (PUVA) in psoriasis could be exerted through induction of apoptosis of keratinocytes and lymphocytes; however, its exact molecular mechanism is still confusing.
Aim
In this study, we evaluated the expression of pro‐apoptotic (P53, Fas and Bax) and anti‐apoptotic (Bcl‐2) proteins correlating it with apoptotic index (AI) and epidermal thickness in psoriatic skin before and after PUVA therapy.
Methods
Lesional and non‐lesional skin biopsy specimens were obtained from 10 patients with generalized plaque psoriasis before and after 8 weeks of PUVA therapy. Histometric measurements of epidermal thickness as well as P53, Fas, Bax and Bcl‐2 expressions were evaluated using immunoperoxidase technique and apoptotic cells were detected by terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method.
Results
After PUVA therapy, the epidermal thickness of psoriatic skin was significantly decreased (P < 0.001) and keratinocytes of psoriatic skin showed significant increased expression of P53 (P < 0.001), Fas (P < 0.001) and Bcl‐2 (P < 0.001) with no significant change in Bax expression (P > 0.05). Apart from significant decrease of Bcl‐2 expression (P = 0.01), no significant difference in all previous markers were encountered in lymphocytes (P53, Fas and Bax; P > 0.05) after PUVA therapy. The AI was significantly increased (P = 0.008) after PUVA therapy especially in lymphocytes (P = 0.002).
Conclusion
The present study suggests that one of the actions of PUVA therapy in psoriasis might be exerted through induction of apoptosis especially of lymphocytes by suppression of Bcl‐2 expression and of keratinocytes through P53 and Fas pathways leading to healing of psoriasis.</description><subject>Adult</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Apoptosis Regulatory Proteins - biosynthesis</subject><subject>Bax protein</subject><subject>Bcl-2</subject><subject>Bcl-2 protein</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>CD95 antigen</subject><subject>Dermatology</subject><subject>DNA nucleotidylexotransferase</subject><subject>Fas antigen</subject><subject>Female</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - radiation effects</subject><subject>Humans</subject><subject>Keratinocytes</subject><subject>Keratinocytes - metabolism</subject><subject>Keratinocytes - pathology</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular modelling</subject><subject>P53</subject><subject>p53 protein</subject><subject>Plaques</subject><subject>psoralen</subject><subject>Psoriasis</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - metabolism</subject><subject>Psoriasis - pathology</subject><subject>Psoriasis. Parapsoriasis. Lichen</subject><subject>PUVA</subject><subject>PUVA Therapy</subject><subject>regulatory proteins</subject><subject>Skin</subject><subject>Skin diseases</subject><subject>Time Factors</subject><subject>U.V. radiation</subject><issn>0905-4383</issn><issn>1600-0781</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNkE9v1DAQxS0EokvhwgdAviAhpJSxnfjPsaraLdKKLhJLuVmziUMN2djYSct-e7Lsttwq5jKj0e_NGz1CXjM4YVN9iDcxnjAOjD8hMyYBClCaPSUzMFAVpdDiiLzI-QcAlCWw5-SIC66ZNGJGVue32I04-NDT0FKMIQ4h-0yT-z52OIS0pTGFwfk-U99P6xxDnx0dAl2uvp7S4cYljFvahkRjDsnjpH5JnrXYZffq0I_J6uL8y9llsbiafzw7XRR1KYAXDde1qUtcc4m6UU5U5TQqpbHkDtcSuOaNkQrXjhutGtdo02pT8hraSqhGHJN3-7vTi79Glwe78bl2XYe9C2O2jOsKjJDM_AeqBJNaVHJC3-_ROoWck2ttTH6DaWsZ2F3idpe4_Zv4BL853B3XG9c8oPcRT8DbA4C5xq5N2Nc-_-Ok0iDlzpXtuTvfue0jlnZ5uVzemxd7jc-D-_2gwfTTSiVUZa8_ze2Cfbu4novPVoo_EtCnjg</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>El-Domyati, Moetaz</creator><creator>Moftah, Noha H.</creator><creator>Nasif, Ghada A.</creator><creator>Abdel-Wahab, Hossam M.</creator><creator>Barakat, Manal T.</creator><creator>Abdel-Aziz, Rasha T.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201302</creationdate><title>Evaluation of apoptosis regulatory proteins in response to PUVA therapy for psoriasis</title><author>El-Domyati, Moetaz ; Moftah, Noha H. ; Nasif, Ghada A. ; Abdel-Wahab, Hossam M. ; Barakat, Manal T. ; Abdel-Aziz, Rasha T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4302-d28c9c4ab26a8d7e354b26778a42eab60282d967abe2987ded89f8942c0f537d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - radiation effects</topic><topic>Apoptosis Regulatory Proteins - biosynthesis</topic><topic>Bax protein</topic><topic>Bcl-2</topic><topic>Bcl-2 protein</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>CD95 antigen</topic><topic>Dermatology</topic><topic>DNA nucleotidylexotransferase</topic><topic>Fas antigen</topic><topic>Female</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - radiation effects</topic><topic>Humans</topic><topic>Keratinocytes</topic><topic>Keratinocytes - metabolism</topic><topic>Keratinocytes - pathology</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular modelling</topic><topic>P53</topic><topic>p53 protein</topic><topic>Plaques</topic><topic>psoralen</topic><topic>Psoriasis</topic><topic>Psoriasis - drug therapy</topic><topic>Psoriasis - metabolism</topic><topic>Psoriasis - pathology</topic><topic>Psoriasis. Parapsoriasis. Lichen</topic><topic>PUVA</topic><topic>PUVA Therapy</topic><topic>regulatory proteins</topic><topic>Skin</topic><topic>Skin diseases</topic><topic>Time Factors</topic><topic>U.V. radiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El-Domyati, Moetaz</creatorcontrib><creatorcontrib>Moftah, Noha H.</creatorcontrib><creatorcontrib>Nasif, Ghada A.</creatorcontrib><creatorcontrib>Abdel-Wahab, Hossam M.</creatorcontrib><creatorcontrib>Barakat, Manal T.</creatorcontrib><creatorcontrib>Abdel-Aziz, Rasha T.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Photodermatology, photoimmunology & photomedicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El-Domyati, Moetaz</au><au>Moftah, Noha H.</au><au>Nasif, Ghada A.</au><au>Abdel-Wahab, Hossam M.</au><au>Barakat, Manal T.</au><au>Abdel-Aziz, Rasha T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of apoptosis regulatory proteins in response to PUVA therapy for psoriasis</atitle><jtitle>Photodermatology, photoimmunology & photomedicine</jtitle><addtitle>Photodermatol. Photoimmunol. Photomed</addtitle><date>2013-02</date><risdate>2013</risdate><volume>29</volume><issue>1</issue><spage>18</spage><epage>26</epage><pages>18-26</pages><issn>0905-4383</issn><eissn>1600-0781</eissn><abstract>Summary
Background
The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. One of the actions of psoralen ultraviolet A (PUVA) in psoriasis could be exerted through induction of apoptosis of keratinocytes and lymphocytes; however, its exact molecular mechanism is still confusing.
Aim
In this study, we evaluated the expression of pro‐apoptotic (P53, Fas and Bax) and anti‐apoptotic (Bcl‐2) proteins correlating it with apoptotic index (AI) and epidermal thickness in psoriatic skin before and after PUVA therapy.
Methods
Lesional and non‐lesional skin biopsy specimens were obtained from 10 patients with generalized plaque psoriasis before and after 8 weeks of PUVA therapy. Histometric measurements of epidermal thickness as well as P53, Fas, Bax and Bcl‐2 expressions were evaluated using immunoperoxidase technique and apoptotic cells were detected by terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method.
Results
After PUVA therapy, the epidermal thickness of psoriatic skin was significantly decreased (P < 0.001) and keratinocytes of psoriatic skin showed significant increased expression of P53 (P < 0.001), Fas (P < 0.001) and Bcl‐2 (P < 0.001) with no significant change in Bax expression (P > 0.05). Apart from significant decrease of Bcl‐2 expression (P = 0.01), no significant difference in all previous markers were encountered in lymphocytes (P53, Fas and Bax; P > 0.05) after PUVA therapy. The AI was significantly increased (P = 0.008) after PUVA therapy especially in lymphocytes (P = 0.002).
Conclusion
The present study suggests that one of the actions of PUVA therapy in psoriasis might be exerted through induction of apoptosis especially of lymphocytes by suppression of Bcl‐2 expression and of keratinocytes through P53 and Fas pathways leading to healing of psoriasis.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><pmid>23281693</pmid><doi>10.1111/phpp.12012</doi><tpages>9</tpages></addata></record> |
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| subjects | Adult Apoptosis Apoptosis - drug effects Apoptosis - radiation effects Apoptosis Regulatory Proteins - biosynthesis Bax protein Bcl-2 Bcl-2 protein Biological and medical sciences Biopsy CD95 antigen Dermatology DNA nucleotidylexotransferase Fas antigen Female Gene Expression Regulation - drug effects Gene Expression Regulation - radiation effects Humans Keratinocytes Keratinocytes - metabolism Keratinocytes - pathology Lymphocytes Male Medical sciences Middle Aged Molecular modelling P53 p53 protein Plaques psoralen Psoriasis Psoriasis - drug therapy Psoriasis - metabolism Psoriasis - pathology Psoriasis. Parapsoriasis. Lichen PUVA PUVA Therapy regulatory proteins Skin Skin diseases Time Factors U.V. radiation |
| title | Evaluation of apoptosis regulatory proteins in response to PUVA therapy for psoriasis |
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