Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo

2008 ◽  
Vol 26 (5) ◽  
pp. 469-477 ◽  
Author(s):  
Anower Hussain Mian ◽  
Hiroaki Saito ◽  
Neil Alles ◽  
Hitoyata Shimokawa ◽  
Kazuhiro Aoki ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Deficient Mice

Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1454-1458 ◽  
Author(s):  
Barbara Zemann ◽  
Bernd Kinzel ◽  
Matthias Müller ◽  
Roland Reuschel ◽  
Diana Mechtcheriakova ◽  
...  
Keyword(s):  
Sphingosine Kinase ◽  
Phase 2 ◽  
Sphingosine Kinase 2 ◽  
Sphingosine 1 Phosphate ◽  
Potent Agonist ◽  
Immunomodulatory Drug ◽  
Secondary Lymphoid Organs ◽  
Deficient Mice

FTY720, a potent immunomodulatory drug in phase 2/3 clinical trials, induces rapid and reversible sequestration of lymphocytes into secondary lymphoid organs, thereby preventing their migration to sites of inflammation. As prerequisite for its function, phosphorylation of FTY720 to yield a potent agonist of the sphingosine-1-phosphate receptor S1P1 is required in vivo, catalyzed by an as-yet-unknown kinase. Here, we report on the generation of sphingosine kinase 2 (SPHK2) knockout mice and demonstrate that this enzyme is essential for FTY720 phosphate formation in vivo. Consequently, administration of FTY720 does not induce lymphopenia in SPHK2-deficient mice. After direct dosage of FTY720 phosphate, lymphopenia is only transient in this strain, indicating that SPHK2 is constantly required to maintain FTY720 phosphate levels in vivo.

scholarly journals Beta 2-microglobulin-dependent NK1.1+ T cells are not essential for T helper cell 2 immune responses.

1996 ◽  
Vol 184 (4) ◽  
pp. 1295-1304 ◽  
Author(s):  
D R Brown ◽  
D J Fowell ◽  
D B Corry ◽  
T A Wynn ◽  
N H Moskowitz ◽  
...  
Keyword(s):  
Immune Responses ◽  
Leishmania Major ◽  
Critical Role ◽  
Airway Hyperreactivity ◽  
T Helper ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Deficient Mice

A number of investigations have established the critical role of interleukin 4 (IL-4) in mediating the development of T helper (Th)2 effector cells in vitro and in vivo. Despite intensive study, the origin of the IL-4 required for Th2 priming and differentiation remains unclear. Natural killer (NK)1.1+ alpha/beta T cell receptor+ T(NT) cells, a unique lineage of cells capable of producing large amounts of IL-4 after activation in vivo, are important candidates for directing Th2 priming. These cells are selected by the nonpolymorphic major histocompatibility complex (MHC) class I molecule, CD1, and are deficient in beta 2-microglobulin (beta 2m)-null mice. We used beta 2m-deficient mice on both BALB/c and C57BL/6 backgrounds to examine their capacity to mount Th2 immune responses after challenge with a number of well-characterized antigens administered by a variety of routes. As assessed by immunization with protein antigen, infection with Leishmania major, embolization with eggs of Schistosoma mansoni, intestinal infection with Nippostrongylus brasiliensis, or induction of airway hyperreactivity to aerosolized antigen, beta 2m-deficient mice developed functional type 2 immune responses that were not substantially different than those in wild-type mice. Production of IL-4 and the generation of immunoglobulin E (IgE) and eosinophil responses were preserved as assessed by a variety of assays. Collectively, these results present a comprehensive analysis of type 2 immune responses in beta 2m-deficient mice, and indicate that beta 2m-dependent NT cells are not required for Th2 development in vivo.

scholarly journals Airway Exposure to Polyethyleneimine Nanoparticles Induces Type 2 Immunity by a Mechanism Involving Oxidative Stress and ATP Release

2021 ◽  
Vol 22 (16) ◽  
pp. 9071
Author(s):  
Yotesawee Srisomboon ◽  
Noriyuki Ohkura ◽  
Koji Iijima ◽  
Takao Kobayashi ◽  
Peter J. Maniak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Responses ◽  
Atp Release ◽  
Bronchial Epithelial ◽  
Pannexin 1 ◽  
In Vivo Experiments ◽  
Atp Efflux ◽  
Deficient Mice

Polyethyleneimine (PEI) induced immune responses were investigated in human bronchial epithelial (hBE) cells and mice. PEI rapidly induced ATP release from hBE cells and pretreatment with glutathione (GSH) blocked the response. PEI activated two conductive pathways, VDAC-1 and pannexin 1, which completely accounted for ATP efflux across the plasma membrane. Moreover, PEI increased intracellular Ca2+ concentration ([Ca2+]i), which was reduced by the pannexin 1 inhibitor, 10Panx (50 μM), the VDAC-1 inhibitor, DIDS (100 μM), and was nearly abolished by pretreatment with GSH (5 mM). The increase in [Ca2+]i involved Ca2+ uptake through two pathways, one blocked by oxidized ATP (oATP, 300 μM) and another that was blocked by the TRPV-1 antagonist A784168 (100 nM). PEI stimulation also increased IL-33 mRNA expression and protein secretion. In vivo experiments showed that acute (4.5 h) PEI exposure stimulated secretion of Th2 cytokines (IL-5 and IL-13) into bronchoalveolar lavage (BAL) fluid. Conjugation of PEI with ovalbumin also induced eosinophil recruitment and secretion of IL-5 and IL-13 into BAL fluid, which was inhibited in IL-33 receptor (ST2) deficient mice. In conclusion, PEI-induced oxidative stress stimulated type 2 immune responses by activating ATP-dependent Ca2+ uptake leading to IL-33 secretion, similar to allergens derived from Alternaria.

Multinucleated Osteoclast Formation In Vivo and In Vitro by P2X7 Receptor-Deficient Mice

2003 ◽  
Vol 13 (2-4) ◽  
pp. 12 ◽  
Author(s):  
Alison Gartland ◽  
Katherine A. Buckley ◽  
Robert A. Hipskind ◽  
M. J. Perry ◽  
J. H. Tobias ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Osteoclast Formation ◽  
Deficient Mice

1906-P: Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients with Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1906-P
Author(s):  
MIKKEL B. CHRISTENSEN ◽  
ASGER LUND ◽  
NIKLAS R. JØRGENSEN ◽  
JENS J. HOLST ◽  
TINA VILSBØLL ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Resorption

scholarly journals Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

Chalcone T4, a novel chalconic compound, inhibits inflammatory bone resorption in vivo and suppresses osteoclastogenesis in vitro

2021 ◽  
Author(s):  
Natalie Aparecida Rodrigues Fernandes ◽  
Angelo Constantino Camilli ◽  
Laura Andrea Gonzalez Maldonado ◽  
Cindy Grace Pérez Pacheco ◽  
Amanda Favoreto Silva ◽  
...  
Keyword(s):  
Bone Resorption
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