Pituitary neuropeptides and B lymphocyte function.

This review discusses the accumulated evidence that pro-opiomelanocortin (POMC) gene products as well as other pituitary neuropeptides derived from related genes (Proenkephalin, PENK; Prodynorphin, PDYN, and Pronociceptin, PNOC) can exert direct effects on B lymphocytes to modulate their functions. We also review the available data on receptor systems that might be involved in the transmission of such hormonal signals to B cells.

Individual pituitary neuropeptides do not recapitulate the effects of repository corticotropin (Acthar®) on human B cells in vitro.

Repository corticotropin injection (RCI), a complex mixture of adrenocorticotropic hormone (ACTH) analogs and other pituitary peptides, has been found to suppress key aspects of gene expression and cellular function in human B lymphocytes in vitro. The present studies reveal that neither individual POMC peptides (α-MSH, ACTH, ACTH, β-endorphin) nor other related pituitary neuropeptides are sufficient to elicit these effects, even though specific receptors capable of transmitting signals from these peptides are expressed by human B cells. RCI's direct effects on human B cells may require complementary signals from multiple components of the preparation.

Repository corticotropin injection reverses critical elements of the TLR9/B cell receptor activation response in human B cells in vitro.

We sought evidence for direct effects of repository corticotropin (RCI; an FDA-approved treatment for selected cases of SLE) on isolated human B lymphocytes activated by engagement of TLR9 and B cell receptors. ODN 2395/αIgM treatment was found to result in induction of 162 distinct mRNAs and suppression of 80 mRNAs at 24 h. RCI treatment resulted in suppression of 14 of the ODN 2395/αIgM -induced mRNAs (mean suppression to 23.

Direct effects of HP Acthar Gel on human B lymphocyte activation in vitro.

Introduction: Both clinical experience and experimental evidence have suggested that Adrenocorticotropic hormone (ACTH) might directly exert immunomodulatory effects not dependent on adrenal steroidogenesis.

Methods: The direct effects of H.P.

Variation in the androgen receptor gene exon 1 CAG repeat correlates with manifestations of autoimmunity in women with lupus.

Clinical and experimental evidence support a role for gonadal steroids in modulating the expression and course of autoimmune diseases such as lupus. Whether or not inherited variation in sensitivity to circulating androgenic hormones could influence the manifestations of such disease is, however, unknown. We sought to determine whether differences in androgen sensitivity conferred by variation in the exon 1 CAG repeat region of the androgen receptor (AR) gene were associated with differences in the clinical or humoral immune manifestations of lupus in a cohort of female subjects.

Glucocorticoid inhibition of activation-induced cytidine deaminase expression in human B lymphocytes.

We examined whether glucocorticoids could modulate the expression of activation-induced cytidine deaminase (AICDA), the principal regulator of the processes of immunoglobulin gene somatic hypermutation and class switch recombination in B lymphocytes. Treatment of human B cells with IL-4 and anti-CD40 antibody for 18-20h resulted in induction of expression of AICDA mRNA by over 10-fold. Dexamethasone at 10nM concentration inhibited AICDA induction by an average of 51.

Estrogen and telomerase in human peripheral blood mononuclear cells.

The enzyme telomerase plays an important role in sustaining the capacity of T lymphocytes for homeostatic replication. Recent data have suggested that gonadal steroids might modulate telomerase expression or activity within these cells. We used quantitative assay techniques for both telomerase mRNA expression and telomerase enzymatic activity to systematically examine the effects of physiologic concentrations of estradiol on human peripheral blood mononuclear cells under basal conditions and under conditions that normally enhance telomerase activity in T lymphocytes.

Protection of rabbits against cutaneous papillomavirus infection using recombinant tobacco mosaic virus containing L2 capsid epitopes.

Cottontail rabbit papillomavirus (CRPV) and rabbit oral papillomavirus (ROPV) represent distantly related, cutaneous and mucosal tissue tropic papillomaviruses respectively that can infect the same host. These two viruses were used to test the effectiveness of an L2 peptide-based vaccine (aa 94-122) that was delivered on the surface of recombinant tobacco mosaic virus (rTMV) particles. Groups of NZW rabbits received combinations of CRPVL2, ROPVL2 and CRPV+ROPVL2 rTMV vaccines, and were then challenged with infectious CRPV and ROPV.