title: Nucleotide oligomerization domains 1 and 2: regulation of expression and function in preadipocytes.
abstract: Translocation of bacteria into the mesenteric fat during intestinal inflammation and the expression of functional TLR1-9 in murine preadipocytes and adipocytes suggest an active role for these cells in innate immunity. The present study focuses on nucleotide oligomerization domains 1 and 2 representing intracellular pattern recognition receptors that sense motifs derived from bacterial peptidoglycans. On mRNA level nucleotide oligomerization domain 1 was found to be constitutively expressed in the preadipocyte cell line 3T3L1 and in primary preadipocytes isolated from murine mesenteric fat, while nucleotide oligomerization domain 2 was only weakly expressed by these cells. Treatment with lactyl-tetra-diaminopimelic acid, muramyl dipeptide, LPS, IL-1beta, and TNF-alpha did not affect cellular nucleotide oligomerization domain 1 mRNA amounts. Except muramyl dipeptide, all factors significantly increased nucleotide oligomerization domain 2 mRNA in mesenteric fat preadipocytes after 4 h. However, specific stimulation of nucleotide oligomerization domain 1 induced IL-6 synthesis in preadipocytes from wild-type or TLR2/4-deficient mice. Confirming nucleotide oligomerization domain 1 specificity, transfection of nucleotide oligomerization domain 1-specific small interfering RNA significantly blocked the effect of lactyl-tetra-diaminopimelic acid on IL-6 production. With specific inhibitors and a NF-kappaB reporter plasmid, nucleotide oligomerization domain 1-mediated activation of NF-kappaB was shown to be responsible for the induction of IL-6 in preadipocytes. In addition, expression of functional nucleotide oligomerization domain 1 could be confirmed in primary human preadipocytes. In summary, we here identified preadipocytes as a novel cell population expressing nucleotide oligomerization domains 1 and 2. Not regulated on transcriptional level, nucleotide oligomerization domain 1 in preadipocytes serves as a sensor for bacterial degradation products and triggers proinflammatory effector responses. Thus, our results further strengthen the allocation of the mesenteric fat and especially of preadipocytes to the innate immune system.
authors: Department of Medicine I, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Thorsten
authors: T
authors: Stroh
authors: Arvind
authors: A
authors: Batra
authors: Rainer
authors: R
authors: Glauben
authors: Inka
authors: I
authors: Fedke
authors: Ulrike
authors: U
authors: Erben
authors: Anjo
authors: A
authors: Kroesen
authors: Markus M
authors: MM
authors: Heimesaat
authors: Stefan
authors: S
authors: Bereswill
authors: Stephen
authors: S
authors: Girardin
authors: Martin
authors: M
authors: Zeitz
authors: Britta
authors: B
authors: Siegmund
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D008643:Mesentery; D051379:Mice; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics* / Q000502:physiology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger