Effect of genetically modified gene tolerant dendritic cell therapy on some blood parameters in experimental mouse arthritis model
Abstract
Rheumatoid
arthritis (RA) is an inflammatory autoimmune disease that causes chronic pain
and joint destruction. T cells activation has an important role in RA
pathogenesis. Activation of T lymphocytes requires the co-stimulatory signals
provided by antigen-presenting cells. T-cell activation without co-stimulation
results in anergy. In this study, to inhibit the activation of T lymphocytes
formed in the experimental arthritis, tolerogenic dendritic cells were aimed to
be obtained by the genetical modification of dendritic cells with CTLA4-KDEL overexpression in endoplasmic
reticulum. Then, RA created animals treated with tolDCs and the effect of
treatment on blood parameters were investigated.
For
this purpose, mouse collagen induced arthritis model was used. The mice with
arthritis were intraarticularly treated with modified tolDCs. It was observed
that the treatment group significantly reversed the increase in the joint
thickness and the increase in the number of white blood cells, especially with
the increase in neutrophils when compared with control groups.
As
a result, genetically modified tolDCs reduced the clinical symptoms of
experimental arthritis and also reversed the changes in blood parameters due to
experimental arthritis in mice.
Keywords
Experimental rheumatoid arthritis CTLA4-KDEL gene therapy Red blood cell count Hemoglobine Hematocrit White blood cell count Formula leucocyte
References
- Buckley CD. Why does chronic inflammatory joint disease persist? Clin Med, 3: 361-366, 2003.
- Cascao R. Rosario HS. Souto-Carneiro MM. Fonseca JE. Neutrophils in rheumatoid arthritis: More than simple final effectors. Autoimmun Rev, 9: 531-535, 2010.
- Cemil BÇ. Ataş H. Psoriasis hastalarında biyolojik tedavinin sistemik inflamatuvar belirteçler ve plateletcrit üzerine etkisi. Dicle Tıp Dergisi, 43: 477-483, 2016.
- Duclos M. Zeidler H. Liman W. Pichler WJ. Rieber P. Peter HH. Characterisation of blood and synovial fluid lymphocytes from patients with rheumatoid arthritis and other joint diseases by monoclonal antibodies (OKT series) and acid alpha-naphthyl esterase staining. Rheumatol Int, 2: 75-82, 1982.
- Gimmi CD. Freeman GJ. Gribben JG. Sugita K. Freedman AS. Morimoto C. Nadler LM. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci USA, 88: 6575-6579, 1991.
- Guvenc G. Karacay M. Akkoc A. Ciftci K. Oral HB. Yalcin M. A new protocol for collagen-induced local arthritis model in Balb/c mice. Turkish Journal of Immunology, 2018 (Baskıda).Harding FA. McArthur JG. Gross JA. Raulet DH. Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature, 356: 607-609, 1992.
- Kilic E. Rezvani A. Toprak AE. Erman H. Ayhan SK. Poyraz E. Ozaras N. Romatoid artritte nötrofil/lenfosit ve platelet/lenfosit oranlarının değerlendirilmesi. Dicle Tıp Dergisi, 43: 241-247, 2016.
- Koo J. Kim S. Jung WJ. Lee YE. Song GG. Kim KS. Kim MY. Increased lymphocyte ınfiltration in rheumatoid arthritis ıs correlated with an ıncrease in lti-like cells in synovial fluid. Immune Netw, 13: 240–248, 2013.
- Kshirsagar AD. Panchal PV. Harle UN. Nanda RK. Shaikh HM. Anti-inflammatory and antiarthritic activity of anthraquinone derivatives in rodents. International Journal of Inflammation, 2014: 690596, 2014.
- Lenschow DJ. Zeng Y. Thistlethwaite JR. Montag A. Brady W. Gibson MG. Linsley PS. Bluestone JA. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science, 257: 789-792, 1992.
- Levent Ö. Ataman Ş. Romatoid artrit tedavisinde yeni yaklaşımlar. Turkiye Klinikleri J PM&R, 2: 124-42, 2002.Linsley PS. Brady W. Urnes M. Grosmaire LS. Damle NK. Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med, 174: 561-569, 1991.
- Linsley PS. Wallace PM. Johnson J. Gibson MG. Greene JL. Ledbetter JA. Singh C. Tepper MA. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science, 257: 792-795, 1992.
- Mellado M. Martinez-Munoz L. Cascio G. Lucas P. Pablos JL. Rodriguez-Frade JM. T cell migration in rheumatoid arthritis. Front Immunol, 6: 384, 2015.
- Mowat AG. Hematologic abnormalities in rheumatoid arthritis. Seminars in Arthritis and Rheumatism, 1: 195–219. 1971.
- Patel MG. Pundarikakshudu K. Anti-arthritic activity of a classical Ayurvedic formulation Vatari Guggulu in rats. J Tradit Complement Med, 6: 389-394, 2015.
- Pincus T. Cronstein B. Braun J. Methotrexate - the anchor drug - an introduction. Clinical and Experimental Rheumatology, 28: 1–2, 2010.
- Singh B. Bani S. Gupta DK. Chandan BK. Kaul A. Anti- inflammatory activity of 'TAF' an active fraction from the plant Barleria prionitis Linn. Journal of Ethnopharmacology, 85: 187–193, 2003.
- Sodhi A. Naik S. Pai A. Anuradha A. Rheumatoid arthritis affecting temporomandibular joint. Contemporary Clinical Dentistry, 6: 124–127, 2015.
- Son YI. Egawa S. Tatsumi T. Redlinger RE. Jr. Kalinski P. Kanto T. A novel bulk-culture method for generating mature dendritic cells from mouse bone marrow cells. J Immunol Methods, 262: 145-157, 2002.
- Sumanth M. Anusha and Swetha S. Elucidation of mechanism of anti- arthritic action of Arthosansar - a polyherbal formulation. Indian Journal of Traditional Knowledge, 11: 704–713, 2012.
- Tak PP. Is early rheumatoid arthritis the same disease process as late rheumatoid arthritis? Best Pract Res Clin Rheumatol, 15: 17-26, 2001.
- Tak PP. Bresnihan B. The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis. Arthritis Rheum, 43: 2619-2633, 2000.
- Trentham DE. Townes AS. Kang AH. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med, 146: 857-868, 1977.
- Wooley PH. Luthra HS. Griffiths MM. Stuart JM. Huse A. David CS. Type II collagen-induced arthritis in mice. IV. Variations in immunogenetic regulation provide evidence for multiple arthritogenic epitopes on the collagen molecule. J Immunol, 135: 2443-2451, 1985.
- Wooley PH. Collagen-induced arthritis in the Mouse. Methods Enzymol, 162: 361-373, 1988.
Effect of genetically modified gene tolerant dendritic cell therapy on some blood parameters in experimental mouse arthritis model
Abstract
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes chronic pain and joint destruction. T cells activation has an important role in RA pathogenesis. Activation of T lymphocytes requires the co-stimulatory signals provided by antigen-presenting cells. T-cell activation without co-stimulation results in anergy. In this study, to inhibit the activation of T lymphocytes formed in the experimental arthritis, tolerogenic dendritic cells were aimed to be obtained by the genetical modification of dendritic cells with CTLA4-KDEL overexpression in endoplasmic reticulum. Then, RA created animals treated with tolDCs and the effect of treatment on blood parameters were investigated.
For this purpose, mouse collagen induced arthritis model was used. The mice with arthritis were intraarticularly treated with modified tolDCs. It was observed that the treatment group significantly reversed the increase in the joint thickness and the increase in the number of white blood cells, especially with the increase in neutrophils when compared with control groups.
As a result, genetically modified tolDCs reduced the clinical symptoms of experimental arthritis and also reversed the changes in blood parameters due to experimental arthritis in mice.
Keywords
Deneysel romatoid artrit CTLA4 tolDH Alyuvar sayısı Hemoglobin Hematokrit Akyuvar sayısı Akyuvar formülü
References
- Buckley CD. Why does chronic inflammatory joint disease persist? Clin Med, 3: 361-366, 2003.
- Cascao R. Rosario HS. Souto-Carneiro MM. Fonseca JE. Neutrophils in rheumatoid arthritis: More than simple final effectors. Autoimmun Rev, 9: 531-535, 2010.
- Cemil BÇ. Ataş H. Psoriasis hastalarında biyolojik tedavinin sistemik inflamatuvar belirteçler ve plateletcrit üzerine etkisi. Dicle Tıp Dergisi, 43: 477-483, 2016.
- Duclos M. Zeidler H. Liman W. Pichler WJ. Rieber P. Peter HH. Characterisation of blood and synovial fluid lymphocytes from patients with rheumatoid arthritis and other joint diseases by monoclonal antibodies (OKT series) and acid alpha-naphthyl esterase staining. Rheumatol Int, 2: 75-82, 1982.
- Gimmi CD. Freeman GJ. Gribben JG. Sugita K. Freedman AS. Morimoto C. Nadler LM. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci USA, 88: 6575-6579, 1991.
- Guvenc G. Karacay M. Akkoc A. Ciftci K. Oral HB. Yalcin M. A new protocol for collagen-induced local arthritis model in Balb/c mice. Turkish Journal of Immunology, 2018 (Baskıda).Harding FA. McArthur JG. Gross JA. Raulet DH. Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature, 356: 607-609, 1992.
- Kilic E. Rezvani A. Toprak AE. Erman H. Ayhan SK. Poyraz E. Ozaras N. Romatoid artritte nötrofil/lenfosit ve platelet/lenfosit oranlarının değerlendirilmesi. Dicle Tıp Dergisi, 43: 241-247, 2016.
- Koo J. Kim S. Jung WJ. Lee YE. Song GG. Kim KS. Kim MY. Increased lymphocyte ınfiltration in rheumatoid arthritis ıs correlated with an ıncrease in lti-like cells in synovial fluid. Immune Netw, 13: 240–248, 2013.
- Kshirsagar AD. Panchal PV. Harle UN. Nanda RK. Shaikh HM. Anti-inflammatory and antiarthritic activity of anthraquinone derivatives in rodents. International Journal of Inflammation, 2014: 690596, 2014.
- Lenschow DJ. Zeng Y. Thistlethwaite JR. Montag A. Brady W. Gibson MG. Linsley PS. Bluestone JA. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science, 257: 789-792, 1992.
- Levent Ö. Ataman Ş. Romatoid artrit tedavisinde yeni yaklaşımlar. Turkiye Klinikleri J PM&R, 2: 124-42, 2002.Linsley PS. Brady W. Urnes M. Grosmaire LS. Damle NK. Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med, 174: 561-569, 1991.
- Linsley PS. Wallace PM. Johnson J. Gibson MG. Greene JL. Ledbetter JA. Singh C. Tepper MA. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science, 257: 792-795, 1992.
- Mellado M. Martinez-Munoz L. Cascio G. Lucas P. Pablos JL. Rodriguez-Frade JM. T cell migration in rheumatoid arthritis. Front Immunol, 6: 384, 2015.
- Mowat AG. Hematologic abnormalities in rheumatoid arthritis. Seminars in Arthritis and Rheumatism, 1: 195–219. 1971.
- Patel MG. Pundarikakshudu K. Anti-arthritic activity of a classical Ayurvedic formulation Vatari Guggulu in rats. J Tradit Complement Med, 6: 389-394, 2015.
- Pincus T. Cronstein B. Braun J. Methotrexate - the anchor drug - an introduction. Clinical and Experimental Rheumatology, 28: 1–2, 2010.
- Singh B. Bani S. Gupta DK. Chandan BK. Kaul A. Anti- inflammatory activity of 'TAF' an active fraction from the plant Barleria prionitis Linn. Journal of Ethnopharmacology, 85: 187–193, 2003.
- Sodhi A. Naik S. Pai A. Anuradha A. Rheumatoid arthritis affecting temporomandibular joint. Contemporary Clinical Dentistry, 6: 124–127, 2015.
- Son YI. Egawa S. Tatsumi T. Redlinger RE. Jr. Kalinski P. Kanto T. A novel bulk-culture method for generating mature dendritic cells from mouse bone marrow cells. J Immunol Methods, 262: 145-157, 2002.
- Sumanth M. Anusha and Swetha S. Elucidation of mechanism of anti- arthritic action of Arthosansar - a polyherbal formulation. Indian Journal of Traditional Knowledge, 11: 704–713, 2012.
- Tak PP. Is early rheumatoid arthritis the same disease process as late rheumatoid arthritis? Best Pract Res Clin Rheumatol, 15: 17-26, 2001.
- Tak PP. Bresnihan B. The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis. Arthritis Rheum, 43: 2619-2633, 2000.
- Trentham DE. Townes AS. Kang AH. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med, 146: 857-868, 1977.
- Wooley PH. Luthra HS. Griffiths MM. Stuart JM. Huse A. David CS. Type II collagen-induced arthritis in mice. IV. Variations in immunogenetic regulation provide evidence for multiple arthritogenic epitopes on the collagen molecule. J Immunol, 135: 2443-2451, 1985.
- Wooley PH. Collagen-induced arthritis in the Mouse. Methods Enzymol, 162: 361-373, 1988.
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Articles |
| Authors | |
| Publication Date | October 15, 2018 |
| Acceptance Date | May 10, 2018 |
| Published in Issue | Year 2018 Volume:37 Number:2 |