Aims: To generate protein microarrays by printing microbial antigens on slides to enable the simultaneous determination in human sera of antibodies directed against Toxoplasma gondii, rubella virus,...
Allergy is estimated to be the sixth leading cause of chronic disease in the US, and the number of people exhibiting symptoms of an allergic response to various natural and synthetic compounds has increased dramatically in the last decade ( 1). The prevalence of food allergies is particularly evident in children; some reports estimate that the frequency of food allergies in infants is 2–5% ( 2). The identification of the specific IgE responsible for the clinical symptoms can be a costly and lengthy procedure. Various immunoassays, such as ELISA ( 3), the Radio Allergo Sorbent Test ( 4), and high-capacity solid-phase tests, e.g., the CAP system (Pharmacia) ( 5), are currently used in the diagnosis of allergies and have the inherent sensitivity and specificity to detect IgE in human serum. However, all of these assays are time-consuming, require large quantities of serum samples, and use poorly characterized antigen preparations. Moreover, none of the assays currently used in the diagnosis of allergies has the throughput to screen for the most common allergens, which are estimated to exceed 300.
Interleukin-1β(IL-1β) is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1βprocessing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1βand its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents. IL-1βis a strong regulator of Brain Natriuretic Peptide (BNP), a hormone involved in cardiovascular homeostasis by guanylyl cyclase Natriuretic Peptide Receptor (NPR-1). An emerging role of BNP in inflammation and immunity, although proposed, remains largely unexplored. Here, we newly demonstrated that, in human THP-1 monocytes, LPS/ATP-induced IL-1βsecretion is strongly inhibited by BNP/NPR-1/cGMP axis at all the molecular mechanisms that tightly control its production and release, NF-kB, ERK 1/2, and all the elements of NALP3/ASC/Caspase-1 inflammasome cascade, and that NALP3 inflammasome inhibition is directly related to BNP deregulatory effect on NF-kB/ERK 1/2 activation. Our findings reveal a novel potent anti-inflammatory and immunomodulatory role for BNP and open new alleys of investigation for a possible employment of this endogenous agent in the treatment of inflammatory/immune-related and IL-1β/NF-kB/ERK1/2/NALP3/ASC/Caspase-1-associated diseases.