Bradykinin 1 receptor blockade subdues systemic autoimmunity, renal inflammation, and blood pressure in murine lupus nephritis 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1107 Immunology

Ling Qin, Yong Du, Huihua Ding, Anam Haque, John Hicks, Claudia Pedroza, Chandra Mohan

Research output: Contribution to journalArticle

Abstract

Objective: The goal of this study was to explore the role of bradykinins and bradykinin 1 receptor (B1R) in murine lupus nephritis. Methods: C57BL/6 and MRL/lpr mice were compared for renal expression of B1R and B2R by western blot and immunohistochemistry. MRL/lpr lupus-prone mice were administered the B1R antagonist, SSR240612 for 12 weeks, and monitored for blood pressure, proteinuria, renal function, and serum autoantibodies. Results: Renal B1R:B2R ratios were significantly upregulated in MRL/lpr mice compared with B6 controls. B1R blockade ameliorated renal pathology lesions, proteinuria, and blood pressure, accompanied by lower serum IgG and anti-dsDNA autoantibody levels, reduced splenic marginal zone B cells and CD4+ T cells, and renal infiltrating CD4+ T cells, macrophages, and neutrophils. Both urine and renal CCL2 and CCL5 chemokines were also decreased in the B1R blocked MRL/lpr mice. Conclusion: Bradykinin receptor B1R blockade ameliorates both systemic immunity and renal inflammation possibly by inhibiting multiple chemokines and renal immune cell infiltration. B1R blockade may be particularly attractive in subjects with concomitant lupus nephritis and hypertension.

LanguageEnglish
Article number12
JournalArthritis Research and Therapy
Volume21
Issue number1
DOIs
StatePublished - Jan 8 2019

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Bradykinin Receptors
Lupus Nephritis
Allergy and Immunology
Autoimmunity
Blood Pressure
Inflammation
Kidney
Inbred MRL lpr Mouse
Health
Proteinuria
Autoantibodies
T-Lymphocytes
Chemokine CCL5
Chemokine CCL2
Bradykinin
Serum
Chemokines
Immunity
Neutrophils
B-Lymphocytes

Keywords

  • Bradykinins
  • Hypertension
  • Kallikrein
  • Lupus nephritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Bradykinin 1 receptor blockade subdues systemic autoimmunity, renal inflammation, and blood pressure in murine lupus nephritis 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1107 Immunology. / Qin, Ling; Du, Yong; Ding, Huihua; Haque, Anam; Hicks, John; Pedroza, Claudia; Mohan, Chandra.

In: Arthritis Research and Therapy, Vol. 21, No. 1, 12, 08.01.2019.

Research output: Contribution to journalArticle

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abstract = "Objective: The goal of this study was to explore the role of bradykinins and bradykinin 1 receptor (B1R) in murine lupus nephritis. Methods: C57BL/6 and MRL/lpr mice were compared for renal expression of B1R and B2R by western blot and immunohistochemistry. MRL/lpr lupus-prone mice were administered the B1R antagonist, SSR240612 for 12 weeks, and monitored for blood pressure, proteinuria, renal function, and serum autoantibodies. Results: Renal B1R:B2R ratios were significantly upregulated in MRL/lpr mice compared with B6 controls. B1R blockade ameliorated renal pathology lesions, proteinuria, and blood pressure, accompanied by lower serum IgG and anti-dsDNA autoantibody levels, reduced splenic marginal zone B cells and CD4+ T cells, and renal infiltrating CD4+ T cells, macrophages, and neutrophils. Both urine and renal CCL2 and CCL5 chemokines were also decreased in the B1R blocked MRL/lpr mice. Conclusion: Bradykinin receptor B1R blockade ameliorates both systemic immunity and renal inflammation possibly by inhibiting multiple chemokines and renal immune cell infiltration. B1R blockade may be particularly attractive in subjects with concomitant lupus nephritis and hypertension.",
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AU - Ding, Huihua

AU - Haque, Anam

AU - Hicks, John

AU - Pedroza, Claudia

AU - Mohan, Chandra

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