Induction of type 1 cytokines during neem leaf glycoprotein assisted carcinoembryonic antigen vaccination is associated with nitric oxide production.
Involvement of the nitric oxide (NO) release in CEAM phi NLGP (carcinoembryonic antigen pulsed macrophages with neem leaf glycoprotein) vaccination and its relationship with vaccine induced type 1 immune response were aimed to study in the present communication. Vaccination with CEAM phi NLGP resulted in macrophage activation as evidenced by its increased number and expression of CD69 marker. Activated macrophages demonstrated upregulation in synthesis of IL-12 and downregulation in IL-10, along with excess IFN gamma production in splenic cells, as evidenced from mRNA analysis. Induction of such type 1 immunity was further confirmed by expression of type 1 specific transcription factor, T-bet and enhancement of intracellular glutathione content. Such vaccination also induced greater nitric oxide (NO) production from macrophages. Dependence of induced type 1 immune response on the NO release and vice versa was studied by in vitro neutralization of IFN gamma/IL-12 and in vivo inhibition of NO production by methylene blue. Obtained results clearly demonstrated the interdependence of two anti-tumor immune functions, namely, NO production and generation of type 1 immune response. Understanding of the mechanism of this NO related immune modulation would have great impact in proposing CEAM phi NLGP vaccine in clinic for the treatment of CEA+ tumors.
Sarkar
Koustav
K
Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata-700026, India.
Bose
Anamika
A
Haque
Enamul
E
Chakraborty
Krishnendu
K
Chakraborty
Tathagata
T
Goswami
Shyamal
S
Ghosh
Diptendu
D
Baral
Rathindranath
R
D000276:Adjuvants, Immunologic; D000818:Animals; D031601:Azadirachta / Q000737:chemistry*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005978:Glutathione / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000008:administration & dosage* / Q000737:chemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D018515:Plant Leaves / Q000737:chemistry / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D000098815:T-bet Transcription Factor
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D006023:Glycoproteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D005978:Glutathione