A novel mutation of indoleamine 2,3-dioxygenase 1 causes a rapid proteasomal degradation and compromises protein function

Mondanelli, Giada; Battista, Valeria Di; Pellanera, Fabrizia; Mammoli, Andrea; Macchiarulo, Antonio; Gargaro, Marco; Mavridou, Elena Eleni; Matteucci, Caterina; Ruggeri, Loredana; Orabona, Ciriana; Volpi, Claudia; Grohmann, Ursula; Mecucci, Cristina

doi:10.1016/j.jaut.2020.102509

Cited by 14 publications

(11 citation statements)

References 43 publications

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“…A bottleneck in developing IDO1 as a predictive biomarker and promising therapeutic target in both T1D and MS is in fact the lack of a genotype‐to‐protein association. To date, a unique rs751360195 single variant in the IDO1 coding sequence has been identified in a 30‐year‐old woman affected by coeliac disorder, selective IgA deficiency, thyroiditis, and thrombocytopenia [ 159 ]. Interestingly, the single nucleotide variant (SNV) rs751360195 encodes a missense mutation (K257E) very closed to the ITIM2 motif that shortens IDO1 half‐life in PBMCs.…”

Section: Physiologic Versus Pathologic Effects Of Ido1mentioning

confidence: 99%

Indoleamine 2,3‐dioxygenase 1 (IDO1): an up‐to‐date overview of an eclectic immunoregulatory enzyme

et al. 2021

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Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the initial rate-limiting step in the degradation of the essential amino acid tryptophan along the kynurenine pathway. When discovered more than 50 years ago, IDO1 was thought to be an effector molecule capable of mediating a survival strategy based on the deprivation of bacteria and tumor cells of the essential amino acid tryptophan. Since 1998, when tryptophan catabolism was discovered to be crucially involved in the maintenance of maternal T cell tolerance, IDO1 has become the focus of several laboratories around the world. Indeed, IDO1 is now considered as an authentic immune regulator not only in pregnancy, but also in autoimmune diseases, chronic inflammation, and tumor immunity. However, in the last years, a bulk of new information − including structural, biologic, and functional evidence − on IDO1 has come to light. For instance, we now know that IDO1 has a peculiar conformational plasticity and, in addition to a complex and highly regulated catalytic activity, is capable of performing a nonenzymic function that reprograms the expression profile of immune cells towards a highly immunoregulatory phenotype. With this State-of-the-Art review, we aimed at gathering the most recent information obtained for this eclectic protein as well as at highlighting the major unresolved questions.

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Section: Physiologic Versus Pathologic Effects Of Ido1mentioning

confidence: 99%

Indoleamine 2,3‐dioxygenase 1 (IDO1): an up‐to‐date overview of an eclectic immunoregulatory enzyme

et al. 2021

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“…After total RNA extraction by TRIzol (Invitrogen, Carlsbad, CA, USA) and reverse transcription to cDNA by QuantiTect Reverse Transcription Kit (Qiagen, Hilden, Germa-nia), a real-time PCR was performed using SYBR Green (Bio-Rad, Hercules, CA, USA) detection and the following specific primers: Gapdh forward 5 -CTGCCCAGAACATCATCCCT-3 ; Gapdh reverse 5 -ACTTGGCAGGTTTCTCCAGG-3 ; Acp5 forward 5 -CTGCCTTGTCAAGA-ACTTGC-3 ; Acp5 reverse 5 -ACCTTTCGTTGATGTCGCAC-3 ; Calcr forward 5 -TCATCAT-CCACCTGGTTGAG-3 ; Calcr reverse 5 -CACAGCCATGACAATCAGAG-3 ; Mmp9 for-ward 5 -GCTGACTACGATAAGGACGGCA-3 ; Mmp9 reverse 5 -GCGGCCCTCAAAGAT-GAACGG-3 ; Ctsk forward 5 -AGAAGACTCACCAGAAGCAG-3 ; and Ctsk reverse 5 -CAGGTTATGGGCAGAGATTTG-3 [27]. Values were calculated as the ratio of the specific gene to Gapdh expression, as determined by the relative quantification method (∆∆CT; means ± SD of triplicate determination) [28].…”

Section: Real-time Pcrmentioning

confidence: 99%

Crocus sativus L. Petal Extract Inhibits Inflammation and Osteoclastogenesis in RAW 264.7 Cell Model

et al. 2022

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The dried stigmas of Crocus sativus L. (Iridaceae) are traditionally processed to produce saffron, a spice widely used as a food coloring and flavoring agent, which is important in the pharmaceutical and textile dye-producing industries. The labor-intensive by-hand harvesting and the use of only a small amount of each flower cause saffron to be the most expensive spice in the world. Crocus sp. petals are by-products of saffron production and represent an interesting raw material for the preparation of extracts intended for health protection in the perspective of a circular economy. In the present study, ethanolic extract from Crocus sativus L. petals (Crocus sativus L. petal extract, CsPE) was tested on macrophages by in vitro models of inflammation and osteoclastogenesis. The extract was found to be endowed with anti-inflammatory activity, significantly reducing the nitric oxide production and IL-6 release by RAW 264.7 murine cells. Moreover, CsPE demonstrated an anti-osteoclastogenic effect, as revealed by a complete inhibition of tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and a decreased expression of key osteoclast-related genes. This study, which focuses on the macrophage as the target cell of the bioactive extract from Crocus sativus L. petals, suggests that the petal by-product of saffron processing can usefully be part of a circular economy network aimed at producing an extract that potentially prevents bone disruption.

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“…Real-time PCR was performed using SYBR Green detection and specific primers listed in Table 1. Values were calculated as the ratio of the specific gene to Gapdh expression, as determined by the relative quantification method (ΔΔCT; means ± SD of triplicate determination) (Mondanelli et al, 2020). IL-6 occurrence in culture supernatants was detected using mouse IL-6 uncoated ELISA Kit (Invitrogen, Carlsbad, CA, United States) as previously described (Mondanelli et al, 2017a) and according to manufacturer's protocol.…”

Section: Real-time Pcr and Il-6 Measurementmentioning

confidence: 99%

Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7

et al. 2021

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Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage in vitro models of inflammation and osteoclastogenesis, we showed that At extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, At demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This At activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL-At exposure. Protective effect of At against bone loss was also enlightened in vivo by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking At decoction, bone and cartilage were well preserved in CIA+At mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to At decoction. Overall, this study enlightens another At cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of At decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis.

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A novel mutation of indoleamine 2,3-dioxygenase 1 causes a rapid proteasomal degradation and compromises protein function

Cited by 14 publications

References 43 publications

Indoleamine 2,3‐dioxygenase 1 (IDO1): an up‐to‐date overview of an eclectic immunoregulatory enzyme

Indoleamine 2,3‐dioxygenase 1 (IDO1): an up‐to‐date overview of an eclectic immunoregulatory enzyme

Crocus sativus L. Petal Extract Inhibits Inflammation and Osteoclastogenesis in RAW 264.7 Cell Model

Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7

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