Nucleosides from Phlebotomus papatasi salivary gland ameliorate murine collagen-induced arthritis by impairing dendritic cell functions

Vanessa Carregaro, Anderson Sá-Nunes, Thiago M. Cunha, Renata Grespan, Carlo J.F. Oliveira, Djalma S. Lima-Junior, Diego L. Costa, Waldiceu A. Verri, Cristiane M. Milanezi, Van My Pham, David Brand, Jesus G. Valenzuela, João S. Silva, José M.C. Ribeiro, Fernando Q. Cunha

Research output: Contribution to journalArticle

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Abstract

Among several pharmacological compounds, Phlebotomine saliva contains substances with anti-inflammatory properties. In this article, we demonstrated the therapeutic activity of salivary gland extract (SGE) of Phlebotomus papatasi in an experimental model of arthritis (collagen-induced arthritis [CIA]) and identified the constituents responsible for such activity. Daily administration of SGE, initiated at disease onset, attenuated the severity of CIA, reducing the joint lesion and proinflammatory cytokine release. In vitro incubation of dendritic cells (DCs) with SGE limited specific CD4+ Th17 cell response. We identified adenosine (ADO) and 5′AMP as the major salivary molecules responsible for anti-inflammatory activities. Pharmacologic inhibition of ADO A2Areceptor or enzymatic catabolism of salivary nucleosides reversed the SGE-induced immunosuppressive effect. Importantly, CD73 (ecto-5′-nucleotidase enzyme) is expressed on DC surface during stage of activation, suggesting that ADO is also generated by 5′AMP metabolism. Moreover, both nucleosides mimicked SGE-induced anti-inflammatory activity upon DC function in vitro and attenuated establishment of CIA in vivo. We reveal that ADO and 5′AMP are present in pharmacological amounts in P. papatasi saliva and act preferentially on DC function, consequently reducing Th17 subset activation and suppressing the autoimmune response. Thus, it is plausible that these constituents might be promising therapeutic molecules to target immune inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)4347-4359
Number of pages13
JournalJournal of Immunology
Volume187
Issue number8
DOIs
StatePublished - Oct 15 2011

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Phlebotomus
Experimental Arthritis
Salivary Glands
Nucleosides
Dendritic Cells
Adenosine
Anti-Inflammatory Agents
Saliva
Pharmacology
Th17 Cells
5'-Nucleotidase
Immune System Diseases
Immunosuppressive Agents
Autoimmunity
Theoretical Models
Joints
Cytokines
Enzymes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Carregaro, V., Sá-Nunes, A., Cunha, T. M., Grespan, R., Oliveira, C. J. F., Lima-Junior, D. S., ... Cunha, F. Q. (2011). Nucleosides from Phlebotomus papatasi salivary gland ameliorate murine collagen-induced arthritis by impairing dendritic cell functions. Journal of Immunology, 187(8), 4347-4359. https://doi.org/10.4049/jimmunol.1003404

Nucleosides from Phlebotomus papatasi salivary gland ameliorate murine collagen-induced arthritis by impairing dendritic cell functions. / Carregaro, Vanessa; Sá-Nunes, Anderson; Cunha, Thiago M.; Grespan, Renata; Oliveira, Carlo J.F.; Lima-Junior, Djalma S.; Costa, Diego L.; Verri, Waldiceu A.; Milanezi, Cristiane M.; Pham, Van My; Brand, David; Valenzuela, Jesus G.; Silva, João S.; Ribeiro, José M.C.; Cunha, Fernando Q.

In: Journal of Immunology, Vol. 187, No. 8, 15.10.2011, p. 4347-4359.

Research output: Contribution to journalArticle

Carregaro, V, Sá-Nunes, A, Cunha, TM, Grespan, R, Oliveira, CJF, Lima-Junior, DS, Costa, DL, Verri, WA, Milanezi, CM, Pham, VM, Brand, D, Valenzuela, JG, Silva, JS, Ribeiro, JMC & Cunha, FQ 2011, 'Nucleosides from Phlebotomus papatasi salivary gland ameliorate murine collagen-induced arthritis by impairing dendritic cell functions', Journal of Immunology, vol. 187, no. 8, pp. 4347-4359. https://doi.org/10.4049/jimmunol.1003404
Carregaro, Vanessa ; Sá-Nunes, Anderson ; Cunha, Thiago M. ; Grespan, Renata ; Oliveira, Carlo J.F. ; Lima-Junior, Djalma S. ; Costa, Diego L. ; Verri, Waldiceu A. ; Milanezi, Cristiane M. ; Pham, Van My ; Brand, David ; Valenzuela, Jesus G. ; Silva, João S. ; Ribeiro, José M.C. ; Cunha, Fernando Q. / Nucleosides from Phlebotomus papatasi salivary gland ameliorate murine collagen-induced arthritis by impairing dendritic cell functions. In: Journal of Immunology. 2011 ; Vol. 187, No. 8. pp. 4347-4359.
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AU - Grespan, Renata

AU - Oliveira, Carlo J.F.

AU - Lima-Junior, Djalma S.

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AU - Milanezi, Cristiane M.

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AU - Valenzuela, Jesus G.

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