Experimental study on constitutions of NZB/W F1 lupus mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To classify NZB/W F1 lupus mice into three different constitutions, i. e. the cold, normal, and hot constitutions, and to prove the objective existence of the difference among them.</p><p><b>METHODS</b>Using the Four Diagnosis Work Station for Mice (founded by Prof. FANG Zhao-qin, the Research Faculty of Experimental Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine), the body weight, the armpit temperature, the heart rate, the 35-s activities, and the color of their tails and claws (r value) were detected. The total weight was calculated according to the formula: The total weight sum = the correction value of claws x 1 + the correction value of tail x 0.2 + the correction value of the armpit temperature x 0.7 + the correction value of heart rate x0. 05 + the number of the quadrant crossing x 0.025. The NZB/W F1 lupus mice were classified into the three different constitutions according to the higher total weight sum, the hotter the constitution, the lower total weight sum, the colder the constitution. The hydroxyproline content, connective tissue growth factor (CTGF), and transforming growth factor-beta1, (TGF-beta1) gene expression difference in the renal tissue were detected and the immunofluorescence staining observed.</p><p><b>RESULTS</b>Among the 158 NZB/W F1 lupus mice, 33 mice were classified into the hot constitution, 34 into the cold constitution, and 91 into the normal constitution. The renal hydroxyproline content in mice of normal and cold constitutions were higher than that of mice of the hot constitution (P<0.01). No statistical difference was shown between mice of the normal constitution and mice of the cold constitution. The CTGF gene expression level was significantly higher in mice of the cold constitution and mice of the hot constitution than in mice of the normal constitution (P<0.05). No significant difference was found between mice of the cold constitution and mice of the hot constitution. Lower level of TGF-beta1, expression existed in mice of the cold constitution than in mice of the normal constitution or mice of the hot constitution, showing insignificant difference. The immunofluorescence stain of the renal tissue among the three constitutions also showed some difference.</p><p><b>CONCLUSION</b>Constitution difference did exist among NZB/W F1 lupus mice.</p>

Effects on prolactin secretion and binding to dopaminergic receptors in sleep-deprived lupus-prone mice

Sleep disturbances have far-reaching effects on the neuroendocrine and immune systems and may be linked to disease manifestation. Sleep deprivation can accelerate the onset of lupus in NZB/NZWF1 mice, an animal model of severe systemic lupus erythematosus. High prolactin (PRL) concentrations are involved in the pathogenesis of systemic lupus erythematosus in human beings, as well as in NZB/NZWF1 mice. We hypothesized that PRL could be involved in the earlier onset of the disease in sleep-deprived NZB/NZWF1 mice. We also investigated its binding to dopaminergic receptors, since PRL secretion is mainly controlled by dopamine. Female NZB/NZWF1 mice aged 9 weeks were deprived of sleep using the multiple platform method. Blood samples were taken for the determination of PRL concentrations and quantitative receptor autoradiography was used to map binding of the tritiated dopaminergic receptor ligands [³H]-SCH23390, [³H]-raclopride and [³H]-WIN35,428 to D1 and D2 dopaminergic receptors and dopamine transporter sites throughout the brain, respectively. Sleep deprivation induced a significant decrease in plasma PRL secretion (2.58 ± 0.95 ng/mL) compared with the control group (25.25 ± 9.18 ng/mL). The binding to D1 and D2 binding sites was not significantly affected by sleep deprivation; however, dopamine transporter binding was significantly increased in subdivisions of the caudate-putamen - posterior (16.52 ± 0.5 vs 14.44 ± 0.6), dorsolateral (18.84 ± 0.7 vs 15.97 ± 0.7) and ventrolateral (24.99 ± 0.5 vs 22.54 ± 0.7 µCi/g), in the sleep-deprived mice when compared to the control group. These results suggest that PRL is not the main mechanism involved in the earlier onset of the disease observed in sleep-deprived NZB/NZWF1 mice and the reduction of PRL concentrations after sleep deprivation may be mediated by modifications in the dopamine transporter sites of the caudate-putamen.

Inducing mutations in the mouse genome with the chemical mutagen ethylnitrosourea

When compared to other model organisms whose genome is sequenced, the number of mutations identified in the mouse appears extremely reduced and this situation seriously hampers our understanding of mammalian gene function(s). Another important consequence of this shortage is that a majority of human genetic diseases still await an animal model. To improve the situation, two strategies are currently used: the first makes use of embryonic stem cells, in which one can induce knockout mutations almost at will; the second consists of a genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes and subsequent identification of the genetic alteration(s). Several projects are now in progress making use of one or the other of these strategies. Here, we report an original effort where we mutagenized BALB/c males, with the mutagen ethylnitrosourea. Offspring of these males were screened for dominant mutations and a three-generation breeding protocol was set to recover recessive mutations. Eleven mutations were identified (one dominant and ten recessives). Three of these mutations are new alleles (Otop1mlh, Foxn1sepe and probably rodador) at loci where mutations have already been reported, while 4 are new and original alleles (carc, eqlb, frqz, and Sacc). This result indicates that the mouse genome, as expected, is far from being saturated with mutations. More mutations would certainly be discovered using more sophisticated phenotyping protocols. Seven of the 11 new mutant alleles induced in our experiment have been localized on the genetic map as a first step towards positional cloning.

La prolactina en el sistema inmunológico: aspectos de síntesis y efectos biológicos / Prolactin in the immune system: synthesis and biological effects

Prolactin (PRL) Is a 23 κDa protein hormone that is produced and secreted by the pituitary lactotrophs. Although PRL was initially regarded as an exclusive pituitary hormone, many nonpituitary tissues were later found to contain and produce this hormone. The most established extrapituitary sites that produce PRL are the decidua, the immune system, brain and endometrium. In the immune system, PRL acts as a cytokine where it plays an important role in human immune responses, including in autoimmune diseases. Here, we will discuss the regulation of PRL gene expression in human lymphocytes and review the functions of PRL made by the immune cells, including its involvement in autoimmunity.

La prolactina es una hormona que fue considerada durante mucho tiempo de origen exclusivamente hipofisario, y cuya función más importante era la promoción de la lactancia. Sin embargo, la prolactina no sólo se sintetiza en diversos sitios del organismo, sino que también participa en una amplia variedad de procesos biológicos. Dentro de los sitios de síntesis extrahipofisarios de esta hormona se encuentran diversas células del sistema inmunológico. A este nivel, la prolactina actúa afectando desde la proliferación celular hasta el estado inmune del individuo. En esta revisión presentamos algunos aspectos relativos a la prolactina de origen linfocitario tales como su síntesis, su participación en el sistema inmunológico y su relación con estados de autoinmunidad.

Experimental study on inhibitory effect of langchuangjing granule on lupoid change of kidney in lupus-prone mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect and mechanism of Langchuangjing Granule (LCJ) in inhibiting the lupoid change of kidney in lupus-prone mice.</p><p><b>METHODS</b>Intervention therapy was applied to three group of BW female mice of lupus, 3 months in age, for 6-12 weeks with LCJ, prednisone and LCJ + prednisone respectively to observe the dynamic development of disease, changes of CD4+, CD8+ and CD54 expression, and the effect on pathology of renal corpuscles.</p><p><b>RESULTS</b>Both western and Chinese medicines can partially improve the symptoms and plasma CD4+ and CD8+ distribution, inhibit the increase of serum ICAM-1 content and the high expression of CD54 in surface of lymphocyte of peripheral blood, suppress the atrophy of renal corpuscles and the proliferation of mesangial cell. The optimal effect was showed by the combination of LCJ and prednisone.</p><p><b>CONCLUSION</b>LCJ could effectively control and improve the genesis and development of lupoid changes in model mice, and regulate the cellular immune function, inhibit the excessive immune reaction, and improve the pathology of lupoid nephritis, it could cooperate with western medicine to give full play of its effective role and show the superiority in treatment.</p>

Prolactina como inmunomodulador / Prolactin how immunomodulator

El propósito de la presente revisión es explorar el papel de la prolactina como inmunomodulador en la respuesta inmune. La prolactina tiene función trófica en la proliferación de los linfocitos. Las células del sistema inmunitario tienen receptores en su superficie para la prolactina, más aún, los linfocitos son capaces de sintetizar y secretar prolactina. Diferentes estados en el nivel de prolactina ejercen una respuesta diferente en el sistema inmunitario, la disminución en la prolactina provoca un deterioro en la respuesta inmunitaria, mientras que el aumento de la prolactina ejerce un incremento de la respuesta inmunitaria. Las alteraciones en la prolactina se han descrito en muchas enfermedades con fondo inmunológico, como el lupus eritematoso sistémico, el síndrome de Reiter, artritis por adyuvantes, uveítis, transplante de órganos. La acumulación de pruebas al momento actual del papel que juega la prolactina como inmunomodulador puede tener un profundo impacto clínico en las enfermedades autoinmunitarias pero aún están en camino de determinarse

Vaccination of different strains of mice against cutaneous leishmaniosis: Usefulnes of membrane antigens encapsulated into liposomes by intraperitoneal and subcutaneous administration

The objetive of this study was to assess the usefulness of parasite-surfase molecules reconstituted into liposomes to vaccinate four diffeent strains of mice (C57BL/10, CBA/ca, C57BL/6 and NZB) with different levels of susceptibility to L. m. mexicana infection and to find out possible increases in specific antibody response after vaccination. but before infection with virulent promastigotes. Mice were vaccinated with parasite membrane antigens incorporated into liposomes and antibody levels were recorded. Vaccination was effective to protect CBA/ca and C57BL/6 but not C57BL/10 mice and NZB animals were naturally resistant. Intraperitoneal (ip) was more efective than the subcutaneus (sc) route if inoculation, and the induction of disease-resistance correlated with the production of IgG anti-Leishmania in CBA/ca, C57BL/6 and C57BL/10 mice

Detection of pre - malignant B-1 cells in NZB mice with a restricted CDR3 / DFL 16 region

The relationship between the immunoglobulin [Ig] nucleotide sequence and the ability of a B cell to develop into a malignant cell was studied in a subset of B cells, B-l cells. B-l cells become malignant in chronic lymphocytic leukemia [CLL] and are responsible for the production of "natural autoantibodies". The autoimmune NZB mouse has been known as a human malignancy and CLL model, because of the age-dependent onset of clonally expanded hyperdiploid B-l cells in these mice. The Ig heavy chain variable region in hyperdiploid B-1 clones from several NZB mice showed common characteristics in the CDR3 shared with fetal B cells: lack of N base insertions and presence of homology sequences at the VH -D-JH junctions that can be encoded by either of the two joined gene segments. Using a degenerative oligoprimer was shown no significant differences in expression of the restricted CDR3/DFL16 region in newborns or in the liver of either strain of mice as young adults. However, the expression of the restricted CDR3/DFL16 in the spleens of young adult NZB was remarkably elevated and showed significant differences from the expression in newborn NZB as well as from young adult and newborn BALB/c mice. It appears that malignant hyperdiploid B-1 cells are derived from fetal B cells. This technique can be used as a molecular marker to demonstrate a relative increase in the expression of this CDR3 in animals pre-destined to develop B-malignancies

Genetics of susceptibility to oral tolerance to ovalbumin

Inbred mouse strains vary widely in their susceptibility to the induction of tolerance following oral (intragastric) adminsitation of ovalbumin. Marked differences were found berween strains that form a congenic pair differing at the H-2 complex: C3H/HeJ (H-2K) and C3H.SW(H2b) - which were very susceptible and resitant to tolerance induction, respectively. In comtrast, no significant differences were found betwwwn a/J(H-2a) and A.BY (H-2b) congenics, which were both susceptible, nor among C57BL/10J congenics, which were uniformly resitant to tolerance induction. We conclude that H-2-linked genes determine tolerance susceptibility in conjunction with background genes