title: IL-4 protein expression and basal activation of Erk in vivo in follicular lymphoma.
abstract: Follicular lymphoma (FL) is characterized by constitutive expression of Bcl-2 as a consequence of t(14;18). Evidence suggests factors in the lymph node microenvironment, related to intratumoral T cells, macrophages, and dendritic cells, play a role in the disease process. We generated proteomic cytokine profiles of FL (N = 50) and follicular hyperplasia (FH; N = 23). A total of 10 cytokines were assayed using ultrasensitive multiplex enzyme-linked immunosorbent assays: IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-12p70, tumor necrosis factor-alpha, and interferon-gamma. Each cytokine showed overall lower protein concentrations in FL, with the exception of IL-4, which was nearly 5 times higher in FL than FH (P = .005). Using reverse-phase protein microarrays (RPMAs), we evaluated the activation state of several intracellular signaling proteins downstream of cytokine receptors. Basal Erk phosphorylation was approximately 4 times greater in FL than FH (P < .001), with similar findings for Mek; Stat-6 showed weak basal phosphorylation that was approximately twice as high in FL than in FH (P = .012). In conclusion, the FL microenvironment contains increased levels of IL-4, with prominent tumor basal phosphorylation of Erk. These findings suggest IL-4, Erk, and possibly Stat-6 may play a role in the biology of FL and may serve as targets for future therapies.
authors.affiliation: Hematopathology Section, Laboratory of Pathology (LP), NIH Clinical Center, Department of Laboratory Medicine, 10 Center Drive, Bldg 10/2C306, Bethesda, MD 20892-1500, USA. calvok@mail.nih.gov
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Calvo
authors.forename: Bhavana
authors.initials: B
authors.lastname: Dabir
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kovach
authors.forename: Christopher
authors.initials: C
authors.lastname: Devor
authors.forename: Russell
authors.initials: R
authors.lastname: Bandle
authors.forename: Amelia
authors.initials: A
authors.lastname: Bond
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Shih
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D008224:Lymphoma, Follicular / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D040081:Protein Array Analysis; D019310:Pseudolymphoma / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism
chemical_list: D016207:Cytokines; C508598:IL4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4; D020928:Mitogen-Activated Protein Kinases