Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2015 Volume 11 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2015 Volume 11 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes

  • Authors:
    • Feng Lv
    • Yang Yu
    • Guihua Wang
    • Junbo Hu
    • Bin Zhang
    • Wei You
    • Jing Wang
  • View Affiliations / Copyright

    Affiliations: Department of Breast Surgery, Henan Provincial People's Hospital, The People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China, Department of Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hebei 430030, P.R. China, Department of Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hebei 430030, P.R. China
  • Pages: 3753-3759
    |
    Published online on: January 12, 2015
       https://doi.org/10.3892/mmr.2015.3184
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

To understand the association between the cytokine network and psoriasis, the present study cultured human keratinocytes (HaCaT cells) and investigated the effects of the phosphatidylinositol‑3‑kinase (PI3K) p55 regulatory subunit (p55PIK), and its N‑terminal 24 amino acids (N24) on the regulation of endotoxin (LPS)‑induced cytokine secretion. The results of the enzyme‑linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction revealed an increased release of the inflammatory cytokines, tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑8 in the HaCaT cells following LPS stimulation. Transfection with the adenovirus (AD)‑N24‑green fluorescent protein (GFP) suppressed the release of these cytokines, whereas AD‑p55PIK‑GFP increased their release. Immunocytochemistry detected a low level of nuclear factor (NF)‑κB p65 staining in quiescent HaCaT cells, which was localized primarily in the cytoplasm. LPS stimulation induced the translocation of NF‑κB p65 protein into the nucleus and intense staining suggested increased expression. Transfection with AD‑N24‑GFP reduced the expression of NF‑κB p65 in the nucleus. Western blot analysis demonstrated that AD‑N24‑GFP downregulated the expression levels of the Toll‑like receptor (TLR)2/TLR4/myeloid differentiation factor 88 (MyD88) pathway components in the HaCaT cells, without affecting the PI3K/Akt signaling pathway. Transfection with AD‑p55PIK‑GFP resulted in an increased expression level of MyD88 protein and phosphorylated Akt. Co‑transfection with AD‑N24‑GFP and AD‑p55PIK‑GFP did not significantly alter the levels of phosphorylated extracellular‑signal‑regulated kinases 1/2, c‑Jun N‑terminal kinases or p38, indicating that AD‑N24‑GFP and AD‑p55PIK‑GFP did not affect the mitogen‑activated protein kinase signaling pathway. In conclusion, AD‑N24‑GFP effectively inhibited the LPS‑induced expression levels of TNF‑α, IL‑6 and IL‑8. The elevated expression of p55PIK synergized with LPS and promoted the release of inflammatory cytokines. AD‑N24‑GFP and AD‑p55PIK‑GFP affected LPS‑induced inflammatory cytokine release in the HaCaT cells through the TLRs/MyD88 signaling pathways.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Cho JH and Gregersen PK: Genomics and the multifactorial nature of human autoimmune disease. N Engl J Med. 365:1612–1623. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Bogdanos DP, Smyk DS, Rigopoulou EI, et al: Twin studies in autoimmune disease: genetics, gender and environment. J Autoimmun. 38:J156–J169. 2012. View Article : Google Scholar

3 

Bruce B1 and Fries JF: The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation. J Rheumatol. 30:167–178. 2003.PubMed/NCBI

4 

Bos JD and De Rie MA: The pathogenesis of psoriasis: Immunological facts and speculations. Immunol Today. 20:40–46. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Lowes MA, Kikuchi T, Fuentes-Duculan J, et al: Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 128:1207–1211. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Cooper KD, Hammerberg C, Baadsgaard O, Elder JT, Chan LS, Sauder DN, Voorhees JJ and Fisher G: IL-1 activity is reduced in psoriatic skin. Decreased IL-1 alpha and increased nonfunctional IL-1 beta. J Immunol. 144:4593–4603. 1990.PubMed/NCBI

7 

Gomi T, Shiohara T, Munakata T, Imanishi K and Nagashima M: Interleukin 1 alpha, tumor necrosis factor alpha and interferon gamma in psoriasis. Arch Dermatol. 127:827–830. 1991. View Article : Google Scholar : PubMed/NCBI

8 

Neuner P, Urbanski A, Trautinger F, Moller A, Kirnbauer R, Kapp A, Schopf E, Schwarz T and Luger TA: Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis. J Invest Dermatol. 97:27–33. 1991. View Article : Google Scholar : PubMed/NCBI

9 

Luger TA and Schwarz T: Evidence for an epidermal cytokine network. J Invest Dermatol. 95:100S–104S. 1990. View Article : Google Scholar : PubMed/NCBI

10 

Gilhar A, Pillar T and Etzioni A: Possible role of cytokines in cellular proliferation of the skin transplanted onto nude mice. Arch Dermatol. 131:38–42. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Stein M, Bernd A, Ramirez-Bosca A, Kippenberger S and Holzmann H: Measurement of anti-inflammatory effects of glucocorticoids on human keratinocytes in vitro. Comparison of normal human keratinocytes with the keratinocyte cell line HaCaT. Arzneimittelforschung. 47:1266–1270. 1997.

12 

Hu J, Xia X, Cheng A, Wang G, Luo X, Reed MF, Fojo T, Oetting A, Gong J and Yen PM: A peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase regulatory subunit: a novel cancer therapy. Mol Cancer Ther. 7:3719–3728. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Mutis T, De Bueger M, Bakker A and Ottenhoff TH: HLA class II+ human keratinocytes present Mycobacterium leprae antigens to CD4+ Th1-like cells. Scand J Immunol. 37:43–51. 1993. View Article : Google Scholar : PubMed/NCBI

14 

Barker JN, Mitra RS, Griffiths CE, Dixit VM and Nickoloff BJ: Keratinocytes as initiators of inflammation. Lancet. 337:211–214. 1991. View Article : Google Scholar : PubMed/NCBI

15 

Akira S: Toll-like receptors and innate immunity. Adv Immunol. 78:1–56. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Su SB, Silver PB, Grajewski RS, Agarwal RK, Tang J, Chan CC and Caspi RR: Essential role of the MyD88 pathway, but nonessential roles of TLRs 2, 4, and 9, in the adjuvant effect promoting Th1-mediated autoimmunity. J Immunol. 175:6303–6310. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, Pearce W, Meek SE, Salpekar A, Waterfield MD, et al: Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science. 297:1031–1034. 2002.PubMed/NCBI

18 

Iwasaki A and Medzhitov R: Toll-like receptor control of the adaptive immune responses. Nat Immunol. 5:987–995. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV and Wu D: Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction. Science. 287:1046–1049. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Puri KD, Doggett TA, Huang CY, Douangpanya J, Hayflick JS, Turner M, Penninger J and Diacovo TG: The role of endothelial PI3Kgamma activity in neutrophil trafficking. Blood. 106:150–157. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Puri KD, Doggett TA, Douangpanya J, Hou Y, Tino WT, Wilson T, Graf T, Clayton E, Turner M, Hayflick JS, et al: Mechanisms and implications of phosphoinositide 3-kinase delta in promoting neutrophil trafficking into inflamed tissue. Blood. 103:3448–3456. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lv F, Yu Y, Wang G, Hu J, Zhang B, You W and Wang J: Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes. Mol Med Rep 11: 3753-3759, 2015.
APA
Lv, F., Yu, Y., Wang, G., Hu, J., Zhang, B., You, W., & Wang, J. (2015). Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes. Molecular Medicine Reports, 11, 3753-3759. https://doi.org/10.3892/mmr.2015.3184
MLA
Lv, F., Yu, Y., Wang, G., Hu, J., Zhang, B., You, W., Wang, J."Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes". Molecular Medicine Reports 11.5 (2015): 3753-3759.
Chicago
Lv, F., Yu, Y., Wang, G., Hu, J., Zhang, B., You, W., Wang, J."Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes". Molecular Medicine Reports 11, no. 5 (2015): 3753-3759. https://doi.org/10.3892/mmr.2015.3184
Copy and paste a formatted citation
x
Spandidos Publications style
Lv F, Yu Y, Wang G, Hu J, Zhang B, You W and Wang J: Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes. Mol Med Rep 11: 3753-3759, 2015.
APA
Lv, F., Yu, Y., Wang, G., Hu, J., Zhang, B., You, W., & Wang, J. (2015). Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes. Molecular Medicine Reports, 11, 3753-3759. https://doi.org/10.3892/mmr.2015.3184
MLA
Lv, F., Yu, Y., Wang, G., Hu, J., Zhang, B., You, W., Wang, J."Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes". Molecular Medicine Reports 11.5 (2015): 3753-3759.
Chicago
Lv, F., Yu, Y., Wang, G., Hu, J., Zhang, B., You, W., Wang, J."Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in human keratinocytes". Molecular Medicine Reports 11, no. 5 (2015): 3753-3759. https://doi.org/10.3892/mmr.2015.3184
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team