Abstract
BackgroundInhibitors of Apoptosis (IAP) family play a critical role in apoptosis and inflammatory response. Neuronal Apoptosis Inhibitory Protein (NAIP), as a member of both IAPs and NLR families (NOD-Like Receptor), is a unique IAP harboring NOD (Nucleotide Oligomerization Domain) and LLR (Leucine Rich Repeat) motifs. Considering these motifs in NAIP, it has been suggested that the main function of NAIP is distinct from other members of IAPs. As a member of NLR, NAIP mediates the assembly of 'Inflammasome' for inflammatory caspase activation. Pathologic expression of NAIP has been reported not only in some infectious and inflammatory diseases but also in some malignancies. However, there is no report to elucidate NAIP expression in lymphomatic malignancies.MethodsIn this study, we examined NAIP protein expression in 101 Formalin-Fixed Paraffin-Embedded blocks including samples from 39 Hodgkin Lymphoma and 23 Non Hodgkin Lymphoma cases in comparison with 39 control samples (30 normal and 9 Reactive Lymphoid Hyperplasia (RLH) lymph nodes) using semi-quantitative immuno-flourecent Staining.ResultsNAIP expression was not statistically different in lymphoma samples neither in HL nor in NHL cases comparing to normal samples. However, we evaluated NAIP expression in normal and RLH lymph nodes. Surprisingly, we have found a statistically significant-difference between the NAIP expression in RLH (M.R of NAIP/GAPDH expression = 0.6365 ± 0.017) and normal lymph node samples (M.R of NAIP/GAPDH expression = 0.5882 ± 0.047) (P < 0.01).ConclusionsThese findings show that the regulation of apoptosis could not be the main function of NAIP in the cell, so the pathologic expression of NAIP is not involved in lymphoma. But, we concluded that the over expression of NAIP has more effective role in the inflammatory response. Also, this study clarifies the NAIP expression level in lymphoma which is required for IAPs profiling in order to be used in potential translational applications of IAPs.
Highlights
Apoptosis is a programmed process leading to cell death which controls the development and homeostasis of multicellular organisms [1]
The lymphoma group consisted of 39 Hodgkin lymphoma (HL) and 23 Non Hodgkin lymphoma (NHL). we considered the available FL cases as a representative of other low grade NHLs as well as the available Diffuse large B cell lymphoma (DLBCL) and Anaplastic large cell lymphoma (ALCL) cases as a representative of other high grade NHLs, hoping to better understanding about main function of Neuronal Apoptosis Inhibitory Protein (NAIP) in Lymphoma context by evaluating the NAIP protein expression
In this study, the expression profiling of NAIP in 39 HL was compared to 39 non-neoplastic lymphoid tissues (30 normal and 9 Reactive lymphoid hyperplasia (RLH) lymph nodes)
Summary
Apoptosis is a programmed process leading to cell death which controls the development and homeostasis of multicellular organisms [1]. The impaired regulation of apoptosis is considered to be a prominent event in the development and progression of tumor cells [7,8] The mechanisms of these defects, have not been fully elucidated. Neuronal Apoptosis Inhibitory Protein (NAIP), as a member of both IAPs and NLR families (NOD-Like Receptor), is a unique IAP harboring NOD (Nucleotide Oligomerization Domain) and LLR (Leucine Rich Repeat) motifs. Considering these motifs in NAIP, it has been suggested that the main function of NAIP is distinct from other members of IAPs. As a member of NLR, NAIP mediates the assembly of ‘Inflammasome’ for inflammatory caspase activation. There is no report to elucidate NAIP expression in lymphomatic malignancies
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