Increased calpain correlates with Th1 cytokine profile in PBMCs from MS patients

Abstract

Multiple sclerosis (MS) is a devastating autoimmune demyelinating disease of the CNS. This study investigated whether expression and activity of the calcium-activated protease calpain correlated with Th1/Th2 dysregulation in MS patients during states of relapse and remission. Calpain expression and activity were significantly increased in peripheral blood mononuclear cells (PBMCs) from MS patients, compared to controls, with the highest expression and activity noted during relapse. Th1 cytokines were highest and Th2 cytokines were lowest in MS patients during relapse. Treatment with calpain inhibitor, calpeptin, decreased Th1 cytokines in PBMCs from MS patients. Calpain inhibitor also reduced degradation of myelin basic protein (MBP) by inhibiting the calpain secreted from MBPspecific T cells. Taken together, these results suggested calpain involvement in Th1/Th2 dysregulation in MS patients.

Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation

“…Increased concentrations of inflammatory mediators such as plasma TNF-α are often associated with the degree of disability as measured with the Expanded Disability Status Scale (EDSS) [12] and predict disease activity [13,14]. Th1-like cytokines, such as IL-2, IL-12, and interferon (IFN)-γ, are often increased in active disease states [8][9][10][11], whereas Th2-like cytokines, including IL-4 and IL-10, may be increased during remission [15][16][17][18]. Nevertheless, concomitant increases in the expression of Th1-and Th2-like cytokines may be present during an acute attack [5,19].…”

Calpains Released by T Lymphocytes Cleave TLR2 To Control IL-17 Expression

“…T lymphocyte activation after TCR/CD3 complex engagement increases calpain expression (5). In turn, calpain activity is involved in T lymphocyte migration (6), secretion of IL-2 and cell surface expression of IL-2R subunit a (CD25) (7), secretion of IFN-g and Th1 commitment (8), and secretion of IL-17 and Th17 commitment (9).…”

Risk of cataract and glaucoma in patients with multiple sclerosis

“…26 Iman et al measured a significantly increased calpain activity and expression in the peripheral blood mononuclear cells of MS patients during a relapse. 8 Calpain 1 (µ-calpain), the lens-specific isoenzyme Lp85, calpain 2 (m-calpain), calpain 3, calpain 10 and the lens-specific Abbreviations: HR, Hazard Ratio; CI, Confidence Interval; N, number of cataract/glaucoma patients # : referent: patients without multiple sclerosis; adjusted for age and gender, smoking, body mass index, systemic glucocorticoids (unless stratified), hypnotics/anxiolytics, anticonvulsants (unless stratified), antidepressants use 6 months prior, diabetes mellitus, chronic obstructive pulmonary disease, cerebrovascular disease, epilepsy and any ocular surgery ever before & : referent: patients without multiple sclerosis; adjusted for age and gender, smoking, body mass index, systemic glucocorticoids (unless stratified), anticonvulsants (unless stratified), serotonin-selective reuptake inhibitors, tricyclic antidepressants, ocular glucocorticoids (unless stratified) use 6 months prior, cerebrovascular disease, epilepsy and any uveitis ever before § : Statistically significant difference (p < 0.05) of the exposure to the medication versus non-exposure to the medication ¥ : Statistically significant difference (p < 0.05) of the exposure to the disease versus non-exposure to the disease isoenzyme Lp82 are known to be active in the lens, with calpain 2 being the most prevalent in mammalian cells. 6,26 In the presence of elevated calcium ion (Ca 2+ ) levels, overactivation of calpains is thought to cause the degradation of lens proteins and changes in the cytoskeletal architecture.…”