ArticleArthritis and rheumatism2013
Enhanced rho-associated protein kinase activation in patients with systemic lupus erythematosus.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 71 citations in OpenAlex.
- Lymphocytes Change Their Phenotype and Function in Systemic Lupus Erythematosus and Lupus Nephritis.International journal of molecular sciences · 2024Review
- Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus.Arthritis research & therapy · 2024Article
- The star target in SLE: IL-17.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Rho GTPases in kidney physiology and diseases.Small GTPases · 2022Article
- Dysregulation and chronicity of pathogenic T cell responses in the pre-diseased stage of lupus.Frontiers in immunology · 2022Review
- A Mechanistic Insight into the Pathogenic Role of Interleukin 17A in Systemic Autoimmune Diseases.Mediators of inflammation · 2022Review
- Rho Kinase regulates neutrophil NET formation that is involved in UVB-induced skin inflammation.Theranostics · 2022Article
- Dysregulated Immunity in Pulmonary Hypertension: From Companion to Composer.Frontiers in physiology · 2022Review
- ROCK2, a critical regulator of immune modulation and fibrosis has emerged as a therapeutic target in chronic graft-versus-host disease.Clinical immunology (Orlando, Fla.) · 2021Review
- The Regulatory Subunit PPP2R2A of PP2A Enhances Th1 and Th17 Differentiation through Activation of the GEF-H1/RhoA/ROCK Signaling Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Coptisine Alleviates Pristane-Induced Lupus-Like Disease and Associated Kidney and Cardiovascular Complications in Mice.Frontiers in pharmacology · 2020Article
- Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus.Frontiers in immunology · 2018Review
- Novel Treatments in Lupus.Frontiers in immunology · 2018Review
- ROCK as a therapeutic target for ischemic stroke.Expert review of neurotherapeutics · 2017Review
- T cells and IL-17 in lupus nephritis.Clinical immunology (Orlando, Fla.) · 2017Review
- Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective.Trends in molecular medicine · 2017Review
- T cells and autoimmune kidney disease.Nature reviews. Nephrology · 2017Review
- Targeting the RhoA-ROCK pathway to reverse T-cell dysfunction in SLE.Annals of the rheumatic diseases · 2017Article
- Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders.Molecules (Basel, Switzerland) · 2017Review
- T cells in Systemic Lupus Erythematosus.Current opinion in immunology · 2016Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveRho-associated protein kinases (ROCKs) have been implicated in the pathogenesis of cardiovascular and renal disorders. We recently showed that ROCKs could regulate the differentiation of murine Th17 cells and the production of interleukin-17 (IL-17) and IL-21, two cytokines associated with systemic lupus erythematosus (SLE). The goal of this study was to assess ROCK activation in human Th17 cells and to evaluate ROCK activity in SLE patients.
methodsAn enzyme-linked immunosorbent assay (ELISA)-based ROCK activity assay was used to evaluate ROCK activity in human cord blood CD4+ T cells differentiated under Th0 or Th17 conditions. We then performed a cross-sectional analysis of 28 SLE patients and 25 healthy matched controls. ROCK activity in peripheral blood mononuclear cell (PBMC) lysates was determined by ELISA. Cytokine and chemokine profiles were analyzed by ELISA.
resultsHuman cord blood CD4+ T cells differentiated under Th17 conditions expressed higher levels of ROCK activity than did CD4+ T cells stimulated under Th0 conditions. Production of IL-17 and IL-21 was inhibited by the addition of a ROCK inhibitor. SLE PBMCs expressed significantly higher levels of ROCK activity than did healthy control PBMCs (1.25 versus 0.56; P = 0.0015). Sixteen SLE patients (57%) expressed high levels of ROCK (optical density at 450 nm >1). Disease duration, lymphocyte count, and azathioprine use were shown to be significant independent predictors of ROCK activity in multivariable analyses.
conclusionConsistent with previous results in the murine system, increased ROCK activation was associated with Th17 cell differentiation. Moreover, enhanced ROCK activity was observed in a subgroup of SLE patients. These data support the concept that the ROCK pathway could represent an important therapeutic target for SLE.
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