Endothelial Fas-Ligand in Inflammatory Bowel Diseases and in Acute Appendicitis

Kokkonen, Tuomo S.; Karttunen, Tuomo J.

doi:10.1369/0022155415608917

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…Indeed, although several anti-CD95L antibodies exist, only one (clone G247-4) gives reliable results in immunohistochemistry experiments ( 54 ). In patients with inflammatory bowel diseases, G247-4 detected CD95L in HEVs expressing HEV markers such as MAdCAM-1 and MECA-79 ( 55 ). Strikingly, CD95L-expressing HEVs observed in cow’s-milk-sensitive enteropathy (CMSE) and celiac disease were surrounded by lymphoid follicles.…”

Section: Drs Belonging To the Tumor Necrosis Factor (Tnf) Receptor (Tmentioning

confidence: 99%

CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

et al. 2017

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Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance. Because mutations of this receptor or its ligand lead to autoimmune disorders such as systemic lupus erythematosus (SLE) and cancers, CD95 and CD95L were initially thought to play a role in immune homeostasis and tumor elimination via apoptotic signaling pathways. However, recent data reveal that CD95 also evokes non-apoptotic signals, promotes inflammation, and contributes to carcinogenesis; therefore, it is difficult to dissect its apoptotic effects from its non-apoptotic effects during pathogenesis of disease. CD95L is cleaved by metalloproteases and so exists in two different forms: a transmembrane form and a soluble ligand (s-CD95L). We recently observed that the soluble ligand is overexpressed in serum from patients with triple-negative breast cancer or SLE, in whom it contributes to disease severity by activating non-apoptotic signaling pathways and promoting either metastatic dissemination or accumulation of certain T cell subsets in damaged organs. Here, we discuss the roles of CD95 in modulating immune functions via induction of mainly non-apoptotic signaling pathways.

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Section: Drs Belonging To the Tumor Necrosis Factor (Tnf) Receptor (Tmentioning

confidence: 99%

CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

et al. 2017

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“…In AA, tumor necrosis factor-α is at the top of the pathway[ 29 , 30 ], and interferon-γ and interleukin-6 play an important role[ 30 , 31 ]. Fas-mediated induction of apoptosis is a major factor in selection of lymphocytes and downregulation of immunological processes, and endothelial Fas-ligand expression is elevated in AA[ 26 ]. AA develops in a progressive and irreversible pathway[ 2 , 16 ], even if the clinical course of AA can be temporarily modified by intentional medications[ 32 ].…”

Section: Pathophysiologymentioning

confidence: 99%

Laparoscopic appendectomy for acute appendicitis: How to discourage surgeons using inadequate therapy

Hori¹,

Machimoto²,

Kadokawa³

et al. 2017

WJG

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Acute appendicitis (AA) develops in a progressive and irreversible manner, even if the clinical course of AA can be temporarily modified by intentional medications. Reliable and real-time diagnosis of AA can be made based on findings of the white blood cell count and enhanced computed tomography. Emergent laparoscopic appendectomy (LA) is considered as the first therapeutic choice for AA. Interval/delayed appendectomy at 6-12 wk after disease onset is considered as unsafe with a high recurrent rate during the waiting time. However, this technique may have some advantages for avoiding unnecessary extended resection in patients with an appendiceal mass. Non-operative management of AA may be tolerated only in children. Postoperative complications increase according to the patient’s factors, and temporal avoidance of emergent general anesthesia may be beneficial for high-risk patients. The surgeon’s skill and cooperation of the hospital are important for successful LA. Delaying appendectomy for less than 24 h from diagnosis is safe. Additionally, a semi-elective manner (i.e., LA within 24 h after onset of symptoms) may be paradoxically acceptable, according to the factors of the patient, physician, and institution. Prompt LA is mandatory for AA. Fortunately, the Japanese government uses a universal health insurance system, which covers LA.

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“…37), which in turn aggregates caspase-8 and caspase-10 to induce apoptosis (38). CD95L is also expressed by endothelial cells lining the blood vessels of patients with tumors and chronic inflammatory disorders (39)(40)(41). These CD95L-expressing endothelial cells seem to behave as a selective immune barrier, killing CD8 T cells while being permissive for Treg cells (41).…”

Section: Introductionmentioning

confidence: 99%