PTX3 Deficiency Promotes Enhanced Accumulation and Function of CD11c+CD11b+ DCs in a Murine Model of Allergic Inflammation

PTX3 is a unique member of the long pentraxins family and plays an indispensable role in regulating the immune system. We previously showed that PTX3 deletion aggravates allergic inflammation via a Th17 -dominant phenotype and enhanced CD4 T cell survival using a murine model of ovalbumin (OVA) induced allergic inflammation. In this study, we identified that upon OVA exposure, increased infiltration of CD11c+CD11b+ dendritic cells (DCs) was observed in the lungs of PTX3-/- mice compared to wild type littermate. Further analysis showed that a short-term OVA exposure led to an increased number of bone marrow common myeloid progenitors (CMP) population concomitantly with increased Ly6Chigh CCR2high monocytes and CD11c+CD11b+ DCs in the lungs. Also, pulmonary CD11c+CD11b+ DCs from OVA-exposed PTX3-/- mice exhibited enhanced expression of maturation markers, chemokines receptors CCR2, and increased OVA uptake and processing compared to wild type controls. Taken together, our data suggest that PTX3 deficiency heightened lung CD11c+CD11b+DC numbers and function, hence exacerbating airway inflammatory response.

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Pentraxin 3 deletion aggravates allergic inflammation through a T H 17-dominant phenotype and enhanced CD4 T-cell survival

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2016.04.063 ◽

2017 ◽

Vol 139 (3) ◽

pp. 950-963.e9 ◽

Cited By ~ 17

Author(s):

Jyoti Balhara ◽

Lianyu Shan ◽

Jingbo Zhang ◽

Anik Muhuri ◽

Andrew J. Halayko ◽

...

Keyword(s):

T Cell ◽

Cell Survival ◽

Allergic Inflammation ◽

Cd4 T Cell ◽

Pentraxin 3 ◽

Dominant Phenotype ◽

T Cell Survival

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Decreased connexin43 expression in the mouse heart potentiates pacing-induced remodeling of repolarizing currents

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.590.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. H1905-H1916 ◽

Cited By ~ 7

Author(s):

Andrianos Kontogeorgis ◽

Xiaodong Li ◽

Eunice Y. Kang ◽

Jonathan E. Feig ◽

Marc Ponzio ◽

...

Keyword(s):

Gap Junction ◽

Ventricular Myocytes ◽

Critical Role ◽

Mouse Heart ◽

Wild Type ◽

Short Term ◽

Wild Type Littermate ◽

Cx43 Expression ◽

Significant Prolongation ◽

Electrophysiological Effects

Gap junction redistribution and reduced expression, a phenomenon termed gap junction remodeling (GJR), is often seen in diseased hearts and may predispose toward arrhythmias. We have recently shown that short-term pacing in the mouse is associated with changes in connexin43 (Cx43) expression and localization but not with increased inducibility into sustained arrhythmias. We hypothesized that short-term pacing, if imposed on murine hearts with decreased Cx43 abundance, could serve as a model for evaluating the electrophysiological effects of GJR. We paced wild-type (normal Cx43 abundance) and heterozygous Cx43 knockout (Cx43+/−; 66% mean reduction in Cx43) mice for 6 h at 10–15% above their average sinus rate. We investigated the electrophysiological effects of pacing on the whole animal using programmed electrical stimulation and in isolated ventricular myocytes with patch-clamp studies. Cx43+/− myocytes had significantly shorter action potential durations (APD) and increased steady-state ( Iss) and inward rectifier ( IK1) potassium currents compared with those of wild-type littermate cells. In Cx43+/− hearts, pacing resulted in a significant prolongation of ventricular effective refractory period and APD and significant diminution of Iss compared with unpaced Cx43+/− hearts. However, these changes were not seen in paced wild-type mice. These data suggest that Cx43 abundance plays a critical role in regulating currents involved in myocardial repolarization and their response to pacing. Our study may aid in understanding how dyssynchronous activation of diseased, Cx43-deficient myocardial tissue can lead to electrophysiological changes, which may contribute to the worsened prognosis often associated with pacing in the failing heart.

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Altered expression and function of canalicular transporters during early development of cholestatic liver injury in Abcb4-deficient mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00334.2013 ◽

2014 ◽

Vol 306 (8) ◽

pp. G670-G676 ◽

Cited By ~ 13

Author(s):

Shi-Ying Cai ◽

Albert Mennone ◽

Carol J. Soroka ◽

James L. Boyer

Keyword(s):

Bile Acid ◽

Apical Membrane ◽

Wild Type ◽

Wild Type Littermate ◽

Altered Expression ◽

Canalicular Transporters ◽

Immunofluorescence Labeling ◽

And Function ◽

Cholestatic Liver Injury ◽

Deficient Mice

Deficiency of ABCB4 is associated with several forms of cholestasis in humans. Abcb4−/− mice also develop cholestasis, but it remains uncertain what role other canalicular transporters play in the development of this disease. We examined the expression of these transporters in Abcb4−/− mice compared with their wild-type littermate controls at ages of 10 days and 3, 6, and 12 wk. Elevated plasma bile acid levels were already detected at 10 days and at all ages thereafter in Abcb4−/− mice. The expression of Bsep, Mrp2, Atp8b1, Abcg5, and Abcg8 liver proteins did not change at 10 days, but Bsep, Mrp2, and Atp8b1 were reduced, whereas Abcg5 and Abcg8 expression were increased in Abcb4−/− mice at all later ages. Lower bile acid concentrations were also detected in the bile of 6-wk-old Abcb4−/− mice. Immunofluorescence labeling revealed distorted canalicular architecture in the liver tissue by 12 wk in Abcb4−/− mice. Whereas Bsep and Mrp2 remained associated with the apical membrane, Atp8b1 was now localized in discrete punctuate structures adjacent to the canalicular membrane in these mice. Expression of Bsep mRNA was increased in the livers of 10-day-old Abcb4−/− mice, whereas Ost-α was decreased. By 12 wk, Bsep, Mrp2, and Abcg5 mRNA were all increased, whereas Ost-α and Ntcp were reduced. These findings indicate that canalicular transporters that determine the formation of bile are altered early in the development of cholestasis in Abcb4−/− mice and may contribute to the pathogenesis of cholestasis in this disorder.

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Early functional muscle regeneration after myotoxic injury in mice is unaffected by nNOS absence

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00096.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. R1358-R1366 ◽

Cited By ~ 10

Author(s):

Jarrod E. Church ◽

Stefan M. Gehrig ◽

Annabel Chee ◽

Timur Naim ◽

Jennifer Trieu ◽

...

Keyword(s):

Muscle Regeneration ◽

Cross Sectional Area ◽

No Production ◽

Sectional Area ◽

Wild Type ◽

Wild Type Littermate ◽

Cross Sectional ◽

Neuronal Subtype ◽

Genetic Deletion ◽

And Function

Nitric oxide (NO) is an important signaling molecule produced in skeletal muscle primarily via the neuronal subtype of NO synthase (NOS1, or nNOS). While many studies have reported NO production to be important in muscle regeneration, none have examined the contribution of nNOS-derived NO to functional muscle regeneration (i.e., restoration of the muscle's ability to produce force) after acute myotoxic injury. In the present study, we tested the hypothesis that genetic deletion of nNOS would impair functional muscle regeneration after myotoxic injury in nNOS−/− mice. We found that nNOS−/− mice had lower body mass, lower muscle mass, and smaller myofiber cross-sectional area and that their tibialis anterior (TA) muscles produced lower absolute tetanic forces than those of wild-type littermate controls but that normalized or specific force was identical between the strains. In addition, muscles from nNOS−/− mice were more resistant to fatigue than those of wild-type littermates ( P < 0.05). To determine whether deletion of nNOS affected muscle regeneration, TA muscles from nNOS−/− mice and wild-type littermates were injected with the myotoxin notexin to cause complete fiber degeneration, and muscle structure and function were assessed at 7 and 10 days postinjury. Myofiber cross-sectional area was lower in regenerating nNOS−/− mice than wild-type controls at 7 and 10 days postinjury; however, contrary to our original hypothesis, no difference in force-producing capacity of the TA muscle was evident between the two groups at either time point. Our findings reveal that nNOS is not essential for functional muscle regeneration after acute myotoxic damage.

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Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice

Molecular Brain ◽

10.1186/s13041-020-00668-4 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Gyu Hyun Kim ◽

Yinhua Zhang ◽

Hyae Rim Kang ◽

Seung-Hyun Lee ◽

Jiwon Shin ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Mitochondrial Fraction ◽

Wild Type ◽

Short Term ◽

Electron Microscopic ◽

Interacting Protein ◽

Short Term Plasticity ◽

Presynaptic Boutons ◽

And Function

Abstract Variants of the cytoplasmic FMR1-interacting protein (CYFIP) gene family, CYFIP1 and CYFIP2, are associated with numerous neurodevelopmental and neuropsychiatric disorders. According to several studies, CYFIP1 regulates the development and function of both pre- and post-synapses in neurons. Furthermore, various studies have evaluated CYFIP2 functions in the postsynaptic compartment, such as regulating dendritic spine morphology; however, no study has evaluated whether and how CYFIP2 affects presynaptic functions. To address this issue, in this study, we have focused on the presynapses of layer 5 neurons of the medial prefrontal cortex (mPFC) in adult Cyfip2 heterozygous (Cyfip2+/−) mice. Electrophysiological analyses revealed an enhancement in the presynaptic short-term plasticity induced by high-frequency stimuli in Cyfip2+/− neurons compared with wild-type neurons. Since presynaptic mitochondria play an important role in buffering presynaptic Ca2+, which is directly associated with the short-term plasticity, we analyzed presynaptic mitochondria using electron microscopic images of the mPFC. Compared with wild-type mice, the number, but not the volume or cristae density, of mitochondria in both presynaptic boutons and axonal processes in the mPFC layer 5 of Cyfip2+/− mice was reduced. Consistent with an identification of mitochondrial proteins in a previously established CYFIP2 interactome, CYFIP2 was detected in a biochemically enriched mitochondrial fraction of the mouse mPFC. Collectively, these results suggest roles for CYFIP2 in regulating presynaptic functions, which may involve presynaptic mitochondrial changes.

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