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1.
Immunol Cell Biol ; 101(5): 444-457, 2023 05.
Article in English | MEDLINE | ID: mdl-36967659

ABSTRACT

Helicobacter pylori (H. pylori) infection can trigger chronic gastric inflammation perpetuated by overactivation of the innate immune system, leading to a cascade of precancerous lesions culminating in gastric cancer. However, key regulators of innate immunity that promote H. pylori-induced gastric pathology remain ill-defined. The innate immune cytosolic DNA sensor absent in melanoma 2 (AIM2) contributes to the pathogenesis of numerous autoimmune and chronic inflammatory diseases, as well as cancers including gastric cancer. We therefore investigated whether AIM2 contributed to the pathogenesis of Helicobacter-induced gastric disease. Here, we reveal that AIM2 messenger RNA and protein expression levels are elevated in H. pylori-positive versus H. pylori-negative human gastric biopsies. Similarly, chronic Helicobacter felis infection in wild-type mice augmented Aim2 gene expression levels compared with uninfected controls. Notably, gastric inflammation and hyperplasia were less severe in H. felis-infected Aim2-/- versus wild-type mice, evidenced by reductions in gastric immune cell infiltrates, mucosal thickness and proinflammatory cytokine and chemokine release. In addition, H. felis-driven proliferation and apoptosis in both gastric epithelial and immune cells were largely attenuated in Aim2-/- stomachs. These observations in Aim2-/- mouse stomachs correlated with decreased levels of inflammasome activity (caspase-1 cleavage) and the mature inflammasome effector cytokine, interleukin-1ß. Taken together, this work uncovers a pathogenic role for the AIM2 inflammasome in Helicobacter-induced gastric disease, and furthers our understanding of the host immune response to a common pathogen and the complex and varying roles of AIM2 at different stages of cancerous and precancerous gastric disease.


Subject(s)
Felis , Helicobacter , Precancerous Conditions , Stomach Neoplasms , Animals , Humans , Mice , Cytokines/metabolism , DNA-Binding Proteins/metabolism , Felis/metabolism , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Helicobacter/metabolism , Inflammasomes/metabolism , Inflammation/pathology , Precancerous Conditions/pathology
2.
J Comp Pathol ; 201: 114-117, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36791602

ABSTRACT

Meningioma is the most frequent intracranial neoplasm in cats. Here we describe the first case of chordoid meningioma (CM), a rare grade II meningioma subtype, in a 5.5-year-old European wildcat (Felis silvestris) from a Swiss zoo. The wildcat was found dead after a clinical history of neurological signs and clinical suspicion of a carcinoma in the right external ear canal with concurrent chronic otitis. Post-mortem examination revealed a large intracranial, extra-axial and intradural neoplasm that invaded into the right ear canal and had histological features compatible with CM, which has been only reported in humans and dogs. Neoplastic cells expressed vimentin but were negative for glial fibrillary acidic protein, S100 and pancytokeratin. Immunohistochemistry revealed epithelial membrane antigen (EMA) expression in neoplastic cells. To the best of our knowledge, we provide the first evidence of EMA expression in feline meningioma.


Subject(s)
Cat Diseases , Dog Diseases , Felis , Meningeal Neoplasms , Meningioma , Cats , Animals , Humans , Dogs , Meningioma/veterinary , Meningeal Neoplasms/veterinary , Mucin-1/metabolism , Immunohistochemistry , Felis/metabolism
3.
PLoS One ; 7(12): e50386, 2012.
Article in English | MEDLINE | ID: mdl-23251368

ABSTRACT

The occurrence of melanism (darkening of the background coloration) is documented in 13 felid species, in some cases reaching high frequencies at the population level. Recent analyses have indicated that it arose multiple times in the Felidae, with three different species exhibiting unique mutations associated with this trait. The causative mutations in the remaining species have so far not been identified, precluding a broader assessment of the evolutionary dynamics of melanism in the Felidae. Among these, the leopard (Panthera pardus) is a particularly important target for research, given the iconic status of the 'black panther' and the extremely high frequency of melanism observed in some Asian populations. Another felid species from the same region, the Asian golden cat (Pardofelis temminckii), also exhibits frequent records of melanism in some areas. We have sequenced the coding region of the Agouti Signaling Protein (ASIP) gene in multiple leopard and Asian golden cat individuals, and identified distinct mutations strongly associated with melanism in each of them. The single nucleotide polymorphism (SNP) detected among the P. pardus individuals was caused by a nonsense mutation predicted to completely ablate ASIP function. A different SNP was identified in P. temminckii, causing a predicted amino acid change that should also induce loss of function. Our results reveal two additional cases of species-specific mutations implicated in melanism in the Felidae, and indicate that ASIP mutations may play an important role in naturally-occurring coloration polymorphism.


Subject(s)
Agouti Signaling Protein/genetics , Felis/genetics , Panthera/genetics , Pigmentation/genetics , Agouti Signaling Protein/metabolism , Animals , Biological Evolution , Felis/metabolism , Molecular Sequence Data , Mutation , Panthera/metabolism , Phenotype , Species Specificity
4.
Article in English | MEDLINE | ID: mdl-21320626

ABSTRACT

Lion (Panthera leo) and caracal (Caracal caracal) skeletal muscle samples from Vastus lateralis, Longissimus dorsi and Gluteus medius were analyzed for fiber type and citrate synthase (CS; EC 2.3.3.1), 3-hydroxyacyl Co A dehydrogenase (3HAD; EC 1.1.1.35), phosphofructokinase-1 (PFK; EC 2.7.1.11), creatine kinase (CK; EC 2.7.3.2), phosphorylase (PHOS; EC 2.4.1.1) and lactate dehydrogenase (LDH; EC 1.1.1.27) activities and compared to human runners, the latter also serving as validation of methodology. Both felids had predominantly type IIx fibers (range 50-80%), whereas human muscle had more types I and IIa. Oxidative capacity of both felids (CS: 5-9 µmol/min/g ww and 3HAD: 1.4-2.6 µmol/min/g ww) was lower than humans, whereas the glycolytic capacity was elevated. LDH activity of caracal (346 ± 81) was higher than lion (227 ± 62 µmol/min/g ww), with human being the lowest (55 ± 17). CK and PHOS activities were also higher in caracal and lion compared to human, but PFK was lower in both felid species. The current data and past research are illustrated graphically showing a strong relationship between type II fibers and sprinting ability in various species. These data on caracal and lion muscles confirm their sprinting behavior.


Subject(s)
Felis/anatomy & histology , Lions/anatomy & histology , Muscle, Skeletal/anatomy & histology , 3-Hydroxyacyl CoA Dehydrogenases/metabolism , Animals , Cats , Citrate (si)-Synthase/metabolism , Creatine Kinase/metabolism , Enzyme Assays , Felis/metabolism , Female , Humans , L-Lactate Dehydrogenase/metabolism , Lions/metabolism , Male , Muscle, Skeletal/enzymology , Myosin Heavy Chains/classification , Myosin Heavy Chains/metabolism , Phosphofructokinases/metabolism , Phosphorylases/metabolism
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