TGN1412, a superagonistic CD28-specific antibody, was shown to require Fc-cross-linking or immobilization as a prerequisite to mediate T-cell proliferation and cytokine release in vitro. We used primary human umbilical vein endothelial cells (HUVECs) to study their ability to induce activation of TGN1412-treated T cells. We confirmed that peripheral primary human T cells do not show activation upon stimulation with soluble TGN1412 alone. Nevertheless, cocultivation of TGN1412-treated T cells with HUVECs induced T-cell activation that was further enhanced using cytokine prestimulated HUVECs. Unexpectedly, Fc-FcγR interaction was dispensable for endothelial cell–mediated proliferation of TGN1412-treated T cells. Transwell-culture assays showed that TGN1412-treated T cells need direct cell-to-cell contact to HUVECs to induce proliferation. We found that costimulatory ICOS-LICOS interaction between T cells and endothelial cells is critically involved in TGN1412-mediated effects. Blocking LICOS reduced TGN1412-mediated T-cell proliferation significantly, whereas recombinant LICOS fully conferred TGN1412-mediated T-cell proliferation. Of note, cytokine stimulation enhanced LICOS expression on HUVECs and ICOS-LICOS interaction up-regulated ICOS expression on TGN1412-treated T cells. Hence, we provide a model of positive feedback conferred by ICOS-LICOS interaction between TGN1412-treated T cells and endothelial cells.

01 Mar 2000·Current BiologyQ1 · BIOLOGY

LICOS, a primordial costimulatory ligand?

Q1 · BIOLOGY

Article

Author: A V Collins ; A Iaboni ; P A van der Merwe ; J A Fennelly ; L M Sparks ; D Brodie ; X N Xu ; S J Davis

In mammals, the classical B7 molecules expressed on antigen-presenting cells, B7-1 (CD80) and B7-2 (CD86), bind the structurally related glycoproteins CD28 and CTLA-4 (CD152), generating costimulatory signals that regulate the activation state of T cells. A recently identified human CD28-like protein, ICOS, also induces costimulatory signals in T cells when crosslinked with antibodies, but it is unclear whether ICOS is part of a B7-mediated regulatory pathway of previously unsuspected complexity, or whether it functions independently and in parallel. Here, we report that, rather than binding B7-1 or B7-2, ICOS binds a new B7-related molecule of previously unknown function that we call LICOS (for ligand of ICOS). At 37 degrees C, LICOS binds only to ICOS but, at lower, non-physiological temperatures, it also binds weakly to CD28 and CTLA-4. Sequence comparisons suggest that LICOS is the homologue of a molecule expressed by avian macrophages and of a murine protein whose expression is induced in non-lymphoid organs by tumour necrosis factor alpha (TNFalpha). Our results define the components of a distinct and novel costimulatory pathway and raise the possibility that LICOS, rather than B7-1 or B7-2, is the contemporary homologue of a primordial vertebrate costimulatory ligand.

01 Sep 1977·Archives internationales de pharmacodynamie et de therapie

Atropine substitutes and the writhing syndrome in mice.

Article

Author: Kelkar, M S

The mouse writhing test has been used to evaluate analgesic drugs. In the present work the protective effect of atropine sulfate and eight of its substitutes was studied against acetic acid-induced writhing in mice. This was compared with the protection afforded by noramidopyrine, a non-narcotic analgesic. Both the time of onset of writhing and the number of writhes over a period of 15 min was recorded. The results seem to indicate some correlation between chemical structure and protective effect. Dicyclomine hydrochloride and orphenadrine hydrochloride produced an effect comparable with that of noramidopyrine, while atropine sulphate, oxyphenonium bromide and piperidolate hydrochloride were less potent. Homatropine methylbromide, mepenzolate methylbromide, amprotropine phosphate and penthienate bromide were ineffective.

100 Deals associated with Piperidolate Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D01165	Piperidolate Hydrochloride	A03AA30	DB13351

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Indication	Country/Location	Organization	Date
Abortion	JP	KYORIN Pharmaceutical Co., Ltd.	07 Apr 1967
Obstetric Labor, Premature	JP	KYORIN Pharmaceutical Co., Ltd.	07 Apr 1967
Spasm	JP	KYORIN Pharmaceutical Co., Ltd.	07 Apr 1967

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