Human Clara cell 10-kDa protein is the counterpart of rabbit uteroglobin.

Mantile, Giuditta; Miele, Lucio; Cordella‐Miele, Eleonora; Singh, Gurmukh; Katyal, Sikandar L.; Mukherjee, Anil B.

doi:10.1016/s0021-9258(20)80734-0

Cited by 123 publications

(12 citation statements)

References 62 publications

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“…We also acknowledge that several additional receptors and multiple mechanisms of action for CC16 have previously been identified (reviewed in Reference 42). Among those previously described mechanisms for CC16 that could also impact phenotypes similar to what we are reporting are phospholipase A2 inhibition (43), accelerated airway epithelial repair (44), and scavenging of reactive oxygen species (34). CC16 is a ligand for ALX (lipoxin receptor A4) and inhibits SSA (serum amyloid-A)-driven inflammation (45).…”

Section: Discussionmentioning

confidence: 67%

CC16 Binding to α₄β₁ Integrin Protects against Mycoplasma pneumoniae Infection

Johnson¹,

Younis

Menghani³

et al. 2021

Am J Respir Crit Care Med

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Rationale: CC16 (club cell secretory protein) is a pneumoprotein produced predominantly by pulmonary club cells. Circulating CC16 is associated with protection from the inception and progression of the two most common obstructive lung diseases (asthma and chronic obstructive pulmonary disease).Objectives: Although exact mechanisms remain elusive, studies consistently suggest a causal role of CC16 in mediating antiinflammatory and antioxidant functions in the lung. We sought to determine any novel receptor systems that could participate in CC16's role in obstructive lung diseases.Methods: Protein alignment of CC16 across species led to the discovery of a highly conserved sequence of amino acids, leucine-valine-aspartic acid (LVD), a known integrin-binding motif. Recombinant CC16 was generated with and without the putative integrin-binding site. A Mycoplasma pneumoniae mouse model and a fluorescent cellular adhesion assay were used to determine the impact of the LVD site regarding CC16 function during live infection and on cellular adhesion during inflammatory conditions.Measurements and Main Results: CC16 bound to integrin a 4 b 1 ), also known as the adhesion molecule VLA-4 (very late antigen 4), dependent on the presence of the LVD integrin-binding motif. During infection, recombinant CC16 rescued lung function parameters both when administered to the lung and intravenously but only when the LVD integrin-binding site was intact; likewise, neutrophil recruitment during infection and leukocyte adhesion were both impacted by the loss of the LVD site.Conclusions: We discovered a novel receptor for CC16, VLA-4, which has important mechanistic implications for the role of CC16 in circulation as well as in the lung compartment.

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Section: Discussionmentioning

confidence: 67%

CC16 Binding to α₄β₁ Integrin Protects against Mycoplasma pneumoniae Infection

Johnson¹,

Younis

Menghani³

et al. 2021

Am J Respir Crit Care Med

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“…The human counterpart of UG was first found in nonciliated bronchiolar Clara cells (Plopper et al, 1980) and was initially named CC10 kDa protein, based on its apparent molecular weight. Subsequently, it was demonstrated that the expression pattern (Peri et al, 1993) and the biochemical properties (Mantile et al, 1993) of CC10 kDa are very similar, if not identical, to those of rabbit UG, thus reinforcing the hypothesis that CC10 kDa can be regarded as the human UG. In particular, Peri et al (1994) have previously demonstrated that UG mRNA and protein are readily detectable in the cycling human endometrium and that the highest levels of expression are observed in the lutheal phase of the menstrual cycle.…”

mentioning

confidence: 80%

Uteroglobin reverts the transformed phenotype in the endometrial adenocarcinoma cell line HEC-1A by disrupting the metabolic pathways generating platelet-activating factor

et al. 2000

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Uteroglobin, originally named blastokinin, is a protein synthesized and secreted by most epithelia, including the endometrium. Uteroglobin has strong anti‐inflammatory properties that appear to be due, at least in part, to its inhibitory effect on the activity of the enzyme phospholipase A2. In addition, recent experimental evidence indicates that uteroglobin exerts antiproliferative and antimetastatic effects in different cancer cells via a membrane receptor. The human endometrial adenocarcinoma cell line HEC‐1A does not express uteroglobin. Thus, we transfected HEC‐1A cells with human uteroglobin cDNA. The transfectants showed a markedly reduced proliferative potential as assessed by impaired plating efficiency as well as by reduced growth in soft agar. Cytofluorimetric analysis clearly indicated that in uteroglobin‐transfected cells the time for completion of the cell cycle was increased. We previously demonstrated that HEC‐1A cells actively synthesize platelet‐activating factor, one of the products of phospholipase A2 activity. In addition, we demonstrated that platelet‐activating factor stimulates the proliferation of these cells through an autocrine loop. In uteroglobin transfectants, the activity of phospholipase A2 and platelet‐activating factor acetyl‐transferase, which are involved in the synthesis of platelet‐activating factor, was significantly reduced compared with wild‐type and vector‐transfected cells (p < 0.05). Our results indicate that enforced expression of uteroglobin in HEC‐1A cells markedly reduced their growth potential and significantly impaired the synthesis of platelet‐activating factor, an autocrine growth factor for these cells. These data suggest that one possible mechanism for the recently observed antineoplastic properties of uteroglobin may be the inhibition of the synthesis of platelet‐activating factor. Int. J. Cancer 88:525–534, 2000. © 2000 Wiley‐Liss, Inc.

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“…Production and Purification of rUG. The production and purification of rUG have been described previously (20,21).…”

Section: Methodsmentioning

confidence: 99%

Uteroglobin Represses Allergen-induced Inflammatory Response by Blocking PGD2 Receptor–mediated Functions

Mandal

Zhang

Ray

et al. 2004

The Journal of Experimental Medicine

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Uteroglobin (UG) is an antiinflammatory protein secreted by the epithelial lining of all organs communicating with the external environment. We reported previously that UG-knockout mice manifest exaggerated inflammatory response to allergen, characterized by increased eotaxin and Th2 cytokine gene expression, and eosinophil infiltration in the lungs. In this study, we uncovered that the airway epithelia of these mice also express high levels of cyclooxygenase (COX)-2, a key enzyme for the production of proinflammatory lipid mediators, and the bronchoalveolar lavage fluid (BALF) contain elevated levels of prostaglandin D2. These effects are abrogated by recombinant UG treatment. Although it has been reported that prostaglandin D2 mediates allergic inflammation via its receptor, DP, neither the molecular mechanism(s) of DP signaling nor the mechanism by which UG suppresses DP-mediated inflammatory response are clearly understood. Here we report that DP signaling is mediated via p38 mitogen–activated protein kinase, p44/42 mitogen–activated protein kinase, and protein kinase C pathways in a cell type–specific manner leading to nuclear factor–κB activation stimulating COX-2 gene expression. Further, we found that recombinant UG blocks DP-mediated nuclear factor–κB activation and suppresses COX-2 gene expression. We propose that UG is an essential component of a novel innate homeostatic mechanism in the mammalian airways to repress allergen-induced inflammatory responses.

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Human Clara cell 10-kDa protein is the counterpart of rabbit uteroglobin.

Cited by 123 publications

References 62 publications

CC16 Binding to α₄β₁ Integrin Protects against Mycoplasma pneumoniae Infection

CC16 Binding to α₄β₁ Integrin Protects against Mycoplasma pneumoniae Infection

Uteroglobin reverts the transformed phenotype in the endometrial adenocarcinoma cell line HEC-1A by disrupting the metabolic pathways generating platelet-activating factor

Uteroglobin Represses Allergen-induced Inflammatory Response by Blocking PGD2 Receptor–mediated Functions

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Human Clara cell 10-kDa protein is the counterpart of rabbit uteroglobin.

Cited by 123 publications

References 62 publications

CC16 Binding to α4β1 Integrin Protects against Mycoplasma pneumoniae Infection

CC16 Binding to α4β1 Integrin Protects against Mycoplasma pneumoniae Infection

Uteroglobin reverts the transformed phenotype in the endometrial adenocarcinoma cell line HEC-1A by disrupting the metabolic pathways generating platelet-activating factor

Uteroglobin Represses Allergen-induced Inflammatory Response by Blocking PGD2 Receptor–mediated Functions

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Product

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CC16 Binding to α₄β₁ Integrin Protects against Mycoplasma pneumoniae Infection

CC16 Binding to α₄β₁ Integrin Protects against Mycoplasma pneumoniae Infection