Therapeutic Effects of Tofacitinib on Pristane-Induced Murine Lupus

LIN, Jiayi; ZHANG, Yaqin; WANG, Meihua; Zhang, Jiatong; Пин, Ли; Cao, Yingping; Yang, Xuwei

doi:10.46497/archrheumatol.2022.8252

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…Nigella sativa L. used in traditional Indonesian medicine, Baicalein—flavonoid derived from the roots of the herbal medicine Scutellaria baicalensis Georgi and 3 β ‐acetyloxy‐oleanolic acid, isolated from the root of Symplocos laurina , also showed an anti‐inflammatory and protective effect on the development of lupus nephritis in this murine model [29, 30]. Other substances, such as tofacitinib and melatonin, also alleviated the progression of pristane‐induced lupus [31–33]. However, the administration of gluten in the diet of the experimental mice had the opposite effect [34].…”

Section: Discussionmentioning

confidence: 99%

Methyl‐supplemented nutrition delays the development of autoimmune disease in pristane‐induced murine lupus

Bradyanova,

Manoylov,

Boneva

et al. 2024

Immunology

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The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl‐supplemented nutrition on the development of SLE was studied in the pristane‐induced mouse model of the disease. The results clearly demonstrated decreased anti‐dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed. The beneficial effect of the diet is due to the methyl‐containing micronutrients with possible anti‐inflammatory and immunomodulating effects on cell proliferation and gene expression. Since these components are responsible for maintaining the physiological methylation level of DNA, the results point to the central role of methylation processes in environmentally triggered lupus. As nutrition represents one of the major epigenetic factors, these micronutrients may be considered novel agents with significant therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Methyl‐supplemented nutrition delays the development of autoimmune disease in pristane‐induced murine lupus

Bradyanova,

Manoylov,

Boneva

et al. 2024

Immunology

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“…Janus kinase (JAK) is involved in diverse immune abnormalities. JAK inhibitors are a potential novel therapy for SLE 30 , 31 .…”

Section: Discussionmentioning

confidence: 99%

Risk factors of diffuse alveolar hemorrhage in Chinese patients with systemic lupus erythematosus

Xu,

Yang,

Cao

et al. 2023

Sci Rep

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This study aimed to investigate the frequency and features of diffuse alveolar hemorrhage (DAH) in Chinese patients with systemic lupus erythematosus (SLE) and evaluate the association of DAH with the features. A total of 943 patients with SLE were categorized into two groups: 896 patients without DAH and 47 patients with DAH. The demographic data, clinical and laboratory findings, and SLE disease activity index 2000 of all patients were statistically analyzed. The DAH frequency in patients with SLE was 4.98%, and the mortality rate of DAH was 42.55%. The clinical features with statistical differences between the two groups were analyzed by multivariate logistic regression, and the results suggested that shorter disease duration [odds ratio (OR): 0.972, 95% confidence interval (CI) 0.946, 0.998], younger age (OR: 0.867, 95% CI 0.764, 0.984), moderate (OR: 25.949, 95% CI 3.316, 203.065) or severe (OR: 24.904, 95% CI 2.675, 231.859) anemia, abnormally elevated levels of urine protein (OR: 10.839, 95% CI 1.351, 86.938) and serum creatinine (OR: 14.534, 95% CI 5.012, 42.142), interstitial lung disease (OR: 6.569, 95% CI 2.053, 21.021), and infection (OR: 8.890, 95% CI 3.580, 22.077) were independent risk factors for the occurrence of DAH in patients with SLE. Moderate or severe anemia was highly suggestive of DAH.

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“…Tofacitinib, a JAK1/3 inhibitor, has been shown to mitigate renal and skin disease in murine lupus by a reduction in IFN gene expression, anti-dsDNA levels, and CD4 + T-cell activation through upregulation of TGFβ type I receptor expression [36][37][38][39]. JAK1/2 inhibition by baricitinib has been shown to attenuate autoimmune features and renal inflammation in murine lupus by suppressing aberrant B-cell activation and podocyte abnormalities [40].…”

Section: Jak Inhibitors In Murine and Experimental Lupusmentioning

confidence: 99%

Targeted Small Molecules for Systemic Lupus Erythematosus: Drugs in the Pipeline

Mok

2023

Drugs

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Despite the uncertainty of the pathogenesis of systemic lupus erythematosus, novel small molecules targeting specific intracellular mechanisms of immune cells are being developed to reverse the pathophysiological processes. These targeted molecules have the advantages of convenient administration, lower production costs, and the lack of immunogenicity. The Janus kinases, Bruton’s tyrosine kinases, and spleen tyrosine kinases are important enzymes for activating downstream signals from various receptors on immune cells that include cytokines, growth factor, hormones, Fc, CD40, and B-cell receptors. Suppression of these kinases impairs cellular activation, differentiation, and survival, leading to diminished cytokine actions and autoantibody secretion. Intracellular protein degradation by immunoproteasomes, levered by the cereblon E3 ubiquitin ligase complex, is an essential process for the regulation of cellular functions and survival. Modulation of the immunoproteasomes and cereblon leads to depletion of long-lived plasma cells, reduced plasmablast differentiation, and production of autoantibodies and interferon-α. The sphingosine 1-phosphate/sphingosine 1-phosphate receptor-1 pathway is responsible for lymphocyte trafficking, regulatory T-cell/Th17 cell homeostasis, and vascular permeability. Sphingosine 1-phosphate receptor-1 modulators limit the trafficking of autoreactive lymphocytes across the blood–brain barrier, increase regulatory T-cell function, and decrease production of autoantibodies and type I interferons. This article summarizes the development of these targeted small molecules in the treatment of systemic lupus erythematosus, and the future prospect for precision medicine.

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Therapeutic Effects of Tofacitinib on Pristane-Induced Murine Lupus

Cited by 5 publications

References 41 publications

Methyl‐supplemented nutrition delays the development of autoimmune disease in pristane‐induced murine lupus

Methyl‐supplemented nutrition delays the development of autoimmune disease in pristane‐induced murine lupus

Risk factors of diffuse alveolar hemorrhage in Chinese patients with systemic lupus erythematosus

Targeted Small Molecules for Systemic Lupus Erythematosus: Drugs in the Pipeline

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