Éditeur(s) : HAL CCSD
Résumé : International audience
The paper deals with iterative schemes for finding a zero of a maximal monotone operator. A combination of the auxiliary principle with the Tikhonov method is considered. Under some assumptions the sequence generated by such an iterative scheme is shown to converge to a solution of the problem that is required to satisfy an associated variational inequality
Lecture notes in economics and mathematical systems

hal-00773198
https://hal.univ-antilles.fr/hal-00773198

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAIL-induced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis.
ISSN: 1350-9047

inserm-00871432
http://www.hal.inserm.fr/inserm-00871432
DOI : 10.1038/cdd.2012.90
PUBMED : 22814620

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Interleukin-33 (IL-33), a cytokine belonging to the IL-1 family, is crucially involved in inflammatory pathologies including liver injury and linked to various modes of cell death. However, a link between IL-33 and necroptosis or programmed necrosis in liver pathology remains elusive. We aimed to investigate the regulation of IL-33 during necroptosis-associated liver injury. The possible regulation of IL-33 during liver injury by receptor-interacting protein kinase 1 (RIPK1) and poly(ADP-ribose) polymerase 1 (PARP-1) was investigated in mice in vivo and in hepatic stellate cells in vitro. The liver immunohistopathology, flow cytometry, serum transaminase measurement, ELISA, and qPCR-based cytokine measurement were carried out. By using a chemical approach, we showed that pretreatment of mice with Necrostatin-1 (Nec-1) (inhibitor of RIPK1) and/or PJ34 (inhibitor of PARP-1) significantly protected mice against concanavalin A (ConA) liver injury (aspartate amino-transferase (AST)/alanine amino-transferase (ALT)) associated with down-regulated hepatocyte-specific IL-33 expression. In contrast, the expression level of most systemic cytokines (except for IL-6) or activation of liver immune cells was not altered by chemical inhibitors rather an increased infiltration of neutrophils in the liver. During polyinosine-polycytidylic acid (Poly(I:C))-induced acute hepatitis, liver injury and hepatocyte-specific IL-33 expression was also inhibited by PJ34 without any protective effect of PJ34 in CCl4-induced liver injury. Moreover, PJ34 down-regulated the protein expression of IL-33 in activated hepatic stellate cells by cocktail of cytokines or staurosporine in vitro. In conclusion, we evidenced that the Nec-1/PJ34 is a potent inhibitor of liver injury and Nec-1/PJ34 down-regulated hepatocyte-specific IL-33 expression in the liver in vivo or in hepatic stellate cells in vitro, suggesting IL-33 as a possible readout of necroptosis-involved liver pathologies. Necroptosis inhibitors can protect mice against liver injury induced by ConA or Poly(I:C). IL-33 expression in liver injury in vivo is inhibited by PJ34. IL-33 expression in hepatic stellate cells in vitro is inhibited by PJ34. Hepatocyte-specific IL-33 expression is down-regulated by Nec-1/PJ34 during hepatitis. IL-33 is a new marker of necroptosis-associated liver injuries.
ISSN: 0946-2716

hal-01134319
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134319
DOI : 10.1007/s00109-015-1270-6
PUBMED : 25747661

Éditeur(s) : HAL CCSD
Résumé : International audience
In the paper the following mixed equilibrium problem in a Hilbert space is considered: find x 2 C such that F(x, x)+hG(x), x−xi 0, 8x 2 C, where C is a nonempty convex closed subset of a real Hilbert space. For its solution a version of the proximal approach is studied. The general proximal method always includes a quadratic term of the kind |x−xn|2, which provides a process of transition from a point xn to a point xn+1. The authors replace this quadratic term by its linearization. Thus, they obtain a method of the kind F(xn+1, x)+hG(xn)+ −1(h 0(xn+1)−h 0(xk)), x−xn+1i 0, 8x 2 C, where h0 is the derivative of a given function on C. It is proved that if the function F(x, y) is monotone and convex in y for any x, F(x, x) = 0, and the operator G(x) is co-coercive, then the method weakly converges in a real Hilbert space to an equilibrium solution. Note that this result will also be true if the co-coercive condition is replaced by a monotonicity property. The Tikhonov regularization method (in the absence of disturbances and calculating auxiliary solutions approximately) is justified and its weak convergence in a Hilbert space is proved. It is known that the proximal method can always be interpreted as an implicit discret approximation of some differential equation or inclusion. Therefore the authors consider a differential inclusion for the extreme mapping. Permitting "-approximation for the function F(x, y) by means of a parametric family F(x, y, ") and assuming the strong monotonicity of the operator @F(x, y, ") (it is a very strong condition), the authors prove the convergence of the trajectory of the differential inclusion to an equilibrium solution.
Ill-posed variational problems and regularization techniques

hal-00773204
https://hal.univ-antilles.fr/hal-00773204

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Hepatocyte death is a central event during liver disease progression, in which immune cells play key roles by activating members of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF), including TNFR1 (TNFRSF1A), Fas (TNFRSF6) and TRAIL-R2 (TNFRSF10B). Receptor Interacting Protein Kinase 1 (RIPK1) emerged as a signaling node downstream of these receptors. In the case of TNFR1, RIPK1 has been demonstrated to paradoxically serve as a scaffold to promote the survival of hepatocytes and as a kinase to kill them. To evaluate whether RIPK1 also protects hepatocytes from death in response to FasL or TRAIL, we took advantage of liver parenchymal cell-specific Ripk1 knockout mice (Ripk1 (LPC-KO)). We found that Ripk1 (LPC-KO) mice, as well as primary hepatocytes derived from them, were more susceptible to Fas-mediated apoptosis than their respective WT counterparts. Fas-induced hepatocyte death was independent of TNF-α signaling. Interestingly, while TRAIL administration did not induce hepatitis in Ripk1 (LPC-KO) mice or in their WT counterparts, its combination with IFN-γ only induced TNF-α dependent apoptosis in the Ripk1 (LPC-KO) mice. Together, our data demonstrate the protective role of RIPK1 downstream of Fas and highlight the general protective function of RIPK1 in hepatocytes exposed to inflammatory conditions, where TNF-α, FasL and/or TRAIL are present.
ISSN: 2045-2322

hal-01579612
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579612
DOI : 10.1038/s41598-017-09789-8
PUBMED : 28835677

Éditeur(s) : HAL CCSD
Résumé : In this note we show that the splitting scheme of Passty [7] as well as the barycentric-proximal method of Lehdili & Lemaire [4] can be used to approximate a zero of the extended sum of maximal monotone operators. When the extended sum is maximal monotone, we extend the convergence result obtained by Lehdili & Lemaire for convex functions to the case of maximal monotone operators. Moreover, we recover the main convergence results by Passty and Lehdili & Lemaire when the pointwise sum of the involved operators is maximal monotone.
https://hal.univ-antilles.fr/hal-00783905

hal-00783905
https://hal.univ-antilles.fr/hal-00783905
https://hal.univ-antilles.fr/hal-00783905/document
https://hal.univ-antilles.fr/hal-00783905/file/10.1.1.165.7044.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
In this note we show that the splitting scheme of Passty [13] as well as the barycentric-proximal method of Lehdili & Lemaire [8] can be used to approximate a zero of the extended sum of maximal monotone operators. When the extended sum is maximal monotone, we generalize a convergence result obtained by Lehdili & Lemaire for convex functions to the case of maximal monotone operators. Moreover, we recover the main convergence results of Passty and Lehdili & Lemaire when the pointwise sum of the involved operators in maximal monotone.
Studies in Computational Mathematics

hal-00778164
https://hal.univ-antilles.fr/hal-00778164
DOI : 10.1016/S1570-579X(01)80022-7