Anupam Mitra

University of California, Davis, Davis, California, United States

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Publications (8)22.44 Total impact

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    ABSTRACT: To quantify the progression and severity of mouse collagen-induced arthritis (CIA) using an in vivo imaging tool, (18) F-fluorodeoxyglucose ((18) F-FDG) PET/CT and validate it against gold standard 'histopathological' evaluation.
    International Journal of Rheumatic Diseases 06/2014; · 1.65 Impact Factor
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    ABSTRACT: Calcitriol is well known for its therapeutic efficacy in psoriasis, but its mechanism of action is still unclear. In this study, we tried to elucidate the precise mechanism of calcitriol for its therapeutic efficacy in psoriasis. Proliferation and apoptosis studies were done to determine the effect of calcitriol on normal human epidermal keratinocytes (NHEKs) and T lymphocytes. To elucidate the effect of Calcitriol on relevant chemokines and epidermal proteins of psoriasis, real-time polymerase chain reaction were done on the modified reconstructed human epidermis (RHE) an in vitro model of psoriasis. All experiments were done in triplicate. Results were expressed as mean ± standard error of mean. In vitro, Calcitriol showed significant inhibition of NHEKs and T lymphocyte proliferation by inducing apoptosis of these cells. Moreover, in an in vitro model of psoriasis (RHE), Calcitriol significantly inhibited relevant gene expression of chemokines (Interleukin-8, Regulated upon Activation Normal T-cell Expressed and Secreted [RANTES]) and psoriasin (S100A7). Here, we observed that Calcitriol inhibits critical pathological events associated with the inflammatory-proliferative cascades of psoriasis. Calcitriol induced apoptosis of NHEKs and T lymphocytes as well as inhibited gene expression of relevant chemokines and epidermal proteins in the in vitro model of psoriasis.
    Indian Journal of Dermatology 03/2014; 59(2):116-22.
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    ABSTRACT: The molecular mechanism responsible for the immunomodulatory effect of 1,25-dihydroxyvitamin D3 (Vit-D) is still not well elucidated. Unavoidable systemic toxicity of Vit-D has encouraged to develop more potent and less toxic Vit-D analogs, such as 1,25-dihydroxyvitamin D3-3-bromoacetate (BE). Our aim was to explore the immunosuppressive effect of BE and its molecular mechanism in autoimmune diseases. Magnetically sorted CD3(+) T cells (T cells) from PBMCs of psoriasis and autoimmune arthritis patients were cultured with/without BE and Vit-D followed by proliferation (MTT, CFSE dilution assays) and apoptosis assays (annexin V). Immunoblot was performed to determine the signaling cascade responsible for the antiproliferative effect. In MTT assay, BE (OD: 0.64±0.08) markedly inhibited the anti-CD3/CD28 stimulated proliferation of T cells (OD: 1.8±0.30, p<0.001) and at equivalent doses, the inhibitory effect was more than that of Vit-D (OD: 0.91±0.11, p<0.05). The antiproliferative effect of BE was extended to activated CD4(+) and CD8(+) memory T cells (CD45RA(-)CD11a(+)) without much effect on the naïve T cells. BE induced more apoptosis of T cells (45.01±4.27%, p<0.001) compared to untreated cells (3.45±1.8%), and the proapoptotic effect was markedly more than that of Vit-D (26.1±2.05%, p<0.05). BE effectively inhibited the anti-CD3/CD28-induced phosphorylation of Akt and mTOR and in both, BE showed more potency than Vit-D (p<0.05). Topical Vit-D is being used successfully in psoriasis for years. However, its potency is less compared to topical corticosteroids. The de novo BE showed significantly more immunosuppression than conventional Vit-D and the immunosuppressive effect is PI3K/Akt/mTOR dependent. Our results indicate that BE could be an effective therapeutic agent for psoriasis and other T-cell-mediated autoimmune disease.
    International immunopharmacology 09/2013; · 2.21 Impact Factor
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    ABSTRACT: The efficacy of 1α,25-dihydroxyvitamin D3 (Vit-D) limits its topical use despite its profound effects on cellular differentiation, proliferation and immunomodulation. Therefore, in search for a more effective analog of Vit-D, in this study we have evaluated the antiproliferative and proapoptotic effects of 1α,25-Dihydroxyvitamin D3-3-bromoacetate (BE). Proliferation and apoptosis studies in normal human epidermal keratinocytes (NHEK) were done by MTT, CFSE dilution and Annexin V assays. Western blot and RT-PCR were done to determine its effect on signal transduction. A reconstructed human epidermis (RHE) model was used to further validate BE's therapeutic role in psoriasis. BE was significantly more potent than an equivalent concentration of Vit-D in inhibiting growth and survival of human keratinocytes. The antimitotic effect was found to be due to inhibition of phosphorylation of AKT and its downstream target, mTOR. In the RHE model, BE reversed IL22-induced psoriasiform changes more effectively than Vit-D. Interestingly, BE inhibited the IL22-induced gene expression of AKT1, MTOR, chemokines (IL-8, RANTES) and psoriasin (S100A7) more significantly than Vit-D. These results suggest the potential of BE as a prospective therapeutic agent for psoriasis.Journal of Investigative Dermatology accepted article preview online, 11 January 2013; doi:10.1038/jid.2013.3.
    Journal of Investigative Dermatology 01/2013; · 6.19 Impact Factor
  • Siba P Raychaudhuri, Anupam Mitra
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    ABSTRACT: Muscle inflammation and weakness are the key features of idiopathic inflammatory myopathies (IIMs). In addition IIMs are frequently associated with cutaneous and pulmonary involvement. In clinical practice the three common inflammatory myopathies we come across are polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). The Bohan and Peter criteria combine clinical, laboratory, and pathologic features to define PM and DM. They did not recognize inclusion body myositis (IBM) or other inflammatory myopathies, such as granulomatous and eosinophilic myositis. Thus the disease spectrum is wide and IIMs are a heterogeneous group of autoimmune disorders. To address these issues in this article we have discussed the currently developing newer classifications of IIMs.
    Indian Journal of Dermatology 09/2012; 57(5):366-70.
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    ABSTRACT: Interleukin 22 (IL-22), a relatively new cytokine has been found to induce significant proliferation of human keratinocytes and fibroblast like synoviocytes (FLS) and thus plays an important role in the pathogenesis of autoimmune diseases like psoriasis and rheumatoid arthritis (RA) which are characterized by hyperproliferation of keratinocytes and FLS respectively. PI3K/Akt/mTOR signaling cascade plays crucial role in cell growth and survival. Therefore our objective was to see the regulatory role of PI3K/Akt/mTOR signaling cascade in IL-22 induced proliferation of keratinocytes and FLS. Normal human epidermal keratinocytes (NHEK) and FLS were isolated from skin of healthy volunteer's undergone plastic surgery and synovial tissue of psoriatic arthritis (PsA) and RA patients respectively. IL-22 induced proliferation of NHEK and FLS was measured by MTT assay. Phosphorylation of Akt/mTOR was determined by western blot assay and further confirmed by real time polymerase chain reaction (RT-PCR). We observed that IL-22 induced significant proliferation of NHEK and FLS which was effectively inhibited by dual kinase (PI3K/mTOR) inhibitor, NVP-BEZ235 and specific mTOR inhibitor, Rapamycin. In NHEK and FLS, IL-22 significantly induced phosphorylation of Akt and mTOR which was effectively blocked by Rapamycin and NVP-BEZ235. Further we did RT-PCR in NHEK and found that IL-22 significantly upregulated AKT1 and MTOR gene. These results show that IL-22 induced proliferation of NHEK and FLS is dependent on PI3K/Akt/mTOR signaling pathway. This novel observation provides the scope to develop new therapeutics targeting PI3K/Akt/mTOR signaling pathway in autoimmune diseases like psoriasis and rheumatoid arthritis.
    Cytokine 07/2012; 60(1):38-42. · 2.52 Impact Factor
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    ABSTRACT: Interleukin-22 (IL-22) is a cytokine of IL-10 family with significant proliferative effect on different cell lines. Immunopathological role of IL-22 has been studied in rheumatoid arthritis (RA) and psoriasis. Here we are reporting the functional role of IL-22 in the inflammatory and proliferative cascades of psoriatic arthritis (PsA). From peripheral blood and synovial fluid (SF) of PsA (n = 15), RA (n = 15) and osteoarthritis (OA, n = 15) patients, mononuclear cells were obtained and magnetically sorted for CD3+ T cells. Fibroblast like synoviocytes (FLS) were isolated from the synovial tissue of PsA (n = 5), RA (n = 5) and OA (n = 5) patients. IL-22 levels in SF and serum were measured by enzyme linked immunosorbent assay (ELISA). Proliferative effect of human recombinant IL-22 (rIL-22) on FLS was assessed by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole) and CFSE dilution (Carboxyfluorescein succinimidyl ester) assays. Expression of IL-22Rα1 in FLS was determined by western blot. IL-22 levels were significantly elevated in SF of PsA patients (17.75 ± 3.46 pg/ml) compared to SF of OA (5.03 ± 0.39 pg/ml), p < 0.001. In MTT and CFSE dilution assays, rIL-22 (MTT, OD: 1.27 ± 0.06) induced significant proliferation of FLS derived from PsA patients compared to media (OD: 0.53 ± 0.02), p < 0.001. In addition, rIL-22 induced significantly more proliferation of FLS in presence of TNF-α. IL-22Rα1 was expressed in FLS of PsA, RA and OA patients. Anti IL-22R antibody significantly inhibited the proliferative effect of rIL-22. Further we demonstrated that activated synovial T cells of PsA and RA patients produced significantly more IL-22 than those of OA patients. SF of PsA patients have higher concentration of IL-22 and rIL-22 induced marked proliferation of PsA derived FLS. Moreover combination of rIL-22 and TNF-α showed significantly more proliferative effect on FLS. IL-22Rα1 was expressed in FLS. Successful inhibition of IL-22 induced FLS proliferation by anti IL-22R antibody suggests that blocking of IL-22/IL-22R interaction may be considered as a novel therapeutic target for PsA.
    Arthritis research & therapy 03/2012; 14(2):R65. · 4.27 Impact Factor
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    ABSTRACT: Increasing evidence supports an important role for inflammation in all phases of atherosclerosis, from initiation of the fatty streak to final culmination in acute coronary syndromes. Numerous inflammatory biomarkers including cell adhesion molecules, cytokines, chemokines, and acute-phase reactants such as fibrinogen, serum amyloid A, and C-reactive protein (CRP) have been shown to predict cardiovascular (CVD) events. Several prospective studies have shown a consistent and robust relationship between levels of high-sensitivity CRP and the risk of future CVD events. Toll-like receptors are pattern recognition receptors and members of the innate immune system that contribute to inflammation and appear to play key roles in atherosclerosis. Lipoprotein-associated phospholipase A2 may also be an independent CVD risk factor. Psoriasis has been associated with an increasing risk for atherosclerosis, including coronary artery disease and stroke. Patients with psoriasis have a 5-year shorter life expectancy, most frequently due to CVD. Psoriasis is associated with a chronic inflammatory state and with elevated levels of CRP and other inflammatory cytokines and these may play a causative role in the increased risk of psoriatic patients for CVD. Patients with psoriasis may represent an emerging risk population and patients with moderate to severe psoriasis should be screened and aggressively treated for CVD risk factors.
    Clinical Reviews in Allergy & Immunology 02/2012; · 5.59 Impact Factor